1,2-dihydropyridine compounds, manufacturing method thereof and use thereof

ABSTRACT

The present invention provides a novel compound having an excellent AMPA receptor inhibitory action and/or kainate inhibitory action. A compound represented by the following formula, a salt thereof or hydrates thereof. 
     
       
         
         
             
             
         
       
     
     In the formula, Q indicates NH, O or S; and R 1 , R 2 , R 3 , R 4  and R 5  are the same as or different from each other and each indicates hydrogen atom, a halogen atom, a C 1-6  alkyl group or a group represented by the formula —X-A (wherein X indicates a single bond, an optionally substituted C 1-6  alkylene group etc.; and A indicates an optionally substituted C 6-14  aromatic hydrocarbocyclic group or 5- to 14-membered aromatic heterocyclic group etc.).

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Divisional of application Ser. No. 11/174,514filed on Jul. 6, 2005, now U.S. Pat. No. 7,563,811, and for whichpriority is claimed under 35 U.S.C. §120. Application Ser. No.11/174,514 is a Divisional of application Ser. No. 10/296,719 filed onNov. 26, 2002, now U.S. Pat. No. 6,949,571, and for which priority isclaimed under 35 USC §120. Application Ser. No. 10/296,719 is thenational phase of PCT International Application No. PCT/JP01/04857 filedon Jun. 8, 2001 under 35 U.S.C. §371. The entire contents of each of theabove-identified applications are hereby incorporated by reference. Thisapplication also claims priority of Application No. 2000-175966 filed inJapan on Jun. 12, 2000 and Application No. 0022483.2 filed in the UnitedKingdom on Sep. 13, 2000 under 35 U.S.C. §119; the entire contents ofall are hereby incorporated by reference.

FIELD OF THE INVENTION

The present invention relates to a novel compound, a salt thereof andhydrates thereof, and to a method for manufacturing the same. Morespecifically, it relates to a pyridone compound, a salt thereof andhydrates thereof which are useful as inhibitors to non-NMDA receptors,particularly to AMPA receptor.

PRIOR ART

Glutamate and aspartate are important amino acids which participate innerve functions such as recognition, memory, movement, respiration,cardiovascular adjustment and sensation and are called excitatoryneurotransmitters as well. In the expression of their physiologicalactivities, an interaction with a specific receptor is important and,generally, two types of receptors—an ion channel type and a G-proteincoupled type—have been known. The former is further classified intoN-methyl-D-aspartate (NMDA) receptor,α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor,kainate receptor, etc. On the other hand, the amino acid as anexcitatory neurotransmitter has been known to induce neurotoxicity by,for example, abnormal excitation of central nerves. It has been notedthat the said toxicity is as serious as being accompanied by the deathof nerve cells causing various nervous diseases. Main nervous diseaseswhich have been known are cerebral ischemia, head injury, spinal cordinjury, Alzheimer's disease, Parkinson's disease, amyotrophic lateralsclerosis (ALS), Huntington's chorea, AIDS nervous disturbance,epilepsy, neurodegeneration observed after the state of hypoxia, mentaldisorder, mobility disturbance, pain, spasticity, nervous disturbance bytoxin in food, various neurodegenerative diseases, various mentaldiseases, chronic pain, migraine, cancer pain and pain caused bydiabetic nervous disturbance. They are serious diseases where manymechanisms of onset, etc. have not been clarified yet and pharmaceuticalagents which are effective for the therapy have not been found yet butit is believed that they are closely related to excessiverelease/accumulation of excitatory neurotransmitters, changes inexpressing pattern of receptors, etc. For example, it has been reportedthat glutamate concentration in cerebrospinal fluid and plasma increasesin stroke, cerebral ischemia, head injury and spinal cord injury(Castillo, J., Dazalos, A. and Noya, M., Lancet, 1997, 346:79-83; etc.).There is a report that neuropathy occurs when glutamate, NMDA, AMPA,kainate, etc. are excessively applied to nerve cells (Meldrum, B., BrainRes. Reviews, 18, 293, 1993). There are reports that, in Alzheimer'sdisease, β-amyloid protein enhances the neurotoxicity of glutamate andthat it promotes the release of glutamate (Arias, C., Arrieta, I. andTapia, R., J. Neurosci. Res., 1995, 41:561-566; etc.). In the case ofParkinson's disease, there are reports that L-dopa hydroxide activatesthe AMPA receptor (Cha, J. J., et. al., Neurosci. Lett., 1991,132:55-58) and enhances the neurotoxicity (Olney, J. W., et. al., 1990,108:269-272; Rosenberg, P. A., et. al., Proc. Natl. Acad. Sci. USA,1991, 88:4865-4869). There is another report that L-dopa promotes thegeneration of free radicals resulting in a rise of oxidative stress(Smith, T. S., et. al., Neuroreport, 1994, 5:1009-1011). In the case ofHuntington's chorea, it is reported that a substance which inhibits therelease of glutamate is effective in improving the symptoms. In the caseof ALS, there are many reports showing the participation of glutamate inits pathology. There are some cases where the AIDS patients suffer fromrecognition nerve function deficiency and, even in such a nerve disease,participation of glutamate is suggested. For example, it is reportedthat gp 120 which is a glycoprotein in an envelope of HIV virussuppresses the uptake of glutamate by astrocytes (Dreyer, E. B., Eur. J.Neurosci., 1995, 7:2502-2507; Ushijima, H., et. al., Eur. J. Neurosci.,1995, 7:1353-1359) while a substance which inhibits the release ofglutamate suppresses the neurodegeneration by gp 120(Sindou, P., et.al., J. Neurosci. 1994, 126:133-137; Muller, W. E. G., et. al., Eur. J.Pharmacol. Molec. Pharmacol., 1992, 226:209-214; Lipton, S. A.,Neurology, 1992, 42:1403-1405). With regard to allergicencephalomyelitis, there is a report that, in the mice where the saidinflammation takes place, enzyme which decomposes glutamate incorporatedfrom outside of cells is deficient (Hardin-Pouzet, H., Glia., 1997,20:79-85). Olivopontocerebellar atrophy is a disease which is sometimescombined with Parkinson's disease and an antibody to GluR2 which is asubunit constituting the AMPA receptor has been found (Gahring, L. C.,Neurology, 1997, 48:494-500) and the relation betweenolivopontocerebellar atrophy and AMPA receptor is suggested. With regardto a report for epilepsy, it is reported that, in the mice which areunable to construct the GluR2 in AMPA receptor, Ca²⁺ permeability of theAMPA receptor increases whereby it is apt to cause a sudden onsetresulting in death (Brusa, R., Science, 1995, 270:1677-1680). Besidesthe above, it is reported that NBQX(2,3-dihydroxy-6-nitro-7-sulfamoylbenz[f]quinoxaline; Sheardown, et al.,Science, 247, 571, 1990) and other inhibiting compounds to AMPAreceptors have antianxiety and anticonvulsant action (J. Pharmacol. Exp.Ther., 260, 742, 1992; Pharmacol. Biochem. Behavior, 1998, 60:119-124)and there are also reports for the connection of AMPA receptor/kainatereceptor with urinary disturbance, drug abuse, pain, etc. (J. Pharmacol.Exp. Ther., 280, 894-904, 1997; Neuroscience Letters, 268:127-130,1999).

It can be expected that the substances showing an antagonistic action toexcitatory neurotransmitter receptors are useful for the therapy of theabove-mentioned nerve diseases. At present, the usefulness of thesubstances having an antagonistic action to non-NMDA receptors such asAMPA receptor and kainate receptor is particularly expected. Forexample, it is reported that inhibitors of the interaction of glutamatewith the AMPA and/or kainate receptor complex are useful in treatingdemyelinating disorders such as encephalitis, acute disseminatedencephalomyelitis, acute demyelinating polyneuropathy (Guillain Barresyndrome), chronic inflammatory demyelinating polyneuropathy, multiplesclerosis, Marchifava-Bignami disease, central pontine myelinolysis,Devic syndrome, Balo disease, HIV- or HTLV-myelopathy, progressivemultifocal leucoencephalopathy, a secondary demyelinating disorder; forexample, CNS lupus erythematodes, polyarteritis nodosa, Sjogrensyndrome, sarcoidosis, isolated cerebral vasculitis, etc. as secondarydemyelinating disorders, etc. in WO00/01376. With regard to the compoundhaving an inhibitory action to AMPA receptor and kainate receptor, thereare reports for the following compounds for example.

(1) Competitive AMPA receptor-inhibiting compounds represented by thefollowing formulae.

(2) Non-competitive AMPA receptor-inhibiting compounds represented bythe following formulae.

(3) Besides the above, there are reports on competitive AMPAreceptor-inhibiting compounds having a quinoxalinedione skeleton in WO94/25469, WO 96/10023, U.S. Pat. No. 5,356,902, etc. and there arereports on non-competitive AMPA receptor-inhibiting compounds in WO95/01357, WO 97/28135, WO 97/18163, WO 97/43276, WO 97/34878, WO98/38173, EP 802195, DE 19643037, etc.

On the other hand, with regard to 1,2-dihydropyridine compounds, therehave been several reports for them such as the compounds represented bythe formula

[in the formula, R is a hydrogen atom, a C₁₋₆ alkyl group, a C₂₋₆alkenyl group, a C₂₋₆ alkynyl group, a C₁₋₆ alkoxy group, etc.; V is CHor N; W is O or S; X is a phenyl group which is unsubstituted orsubstituted with one or more group(s) selected from a C₁₋₆ alkyl group,CF₃, a cyano group, a nitro group, halogen, etc. or an aromatic heterogroup which is substituted with one or more group(s) selected from aC₁₋₆ alkyl group, CF₃, halogen, etc.; Y is a hydrogen atom, a C₁₋₆ alkylgroup, a C₂₋₆ alkenyl group, a C₂₋₆ alkynyl group, an aryl group, etc.;and Z is halogen, a C₃₋₆ cycloalkyl group, a C₁₋₆ alkylthio group, aC₂₋₆ alkenylthio group, an aryl group, etc.] or salts thereof as aligand for GABA_(A)α subunit in WO 98/55480 and the compoundsrepresented by the formula

[in the formula, n is 0, 1, 2, 3, 4 or 5; X is a hydrogen atom, a C₁₋₄alkyl group, a C₁₋₄ alkoxy group, a trifluoromethyl group, atrifluoromethoxy group or halogen; A is an amino group, a C₁₋₄alkylamino group, a C₁₋₄ dialkylamino group, a morpholino group, apiperidino group or a pyrrolidino group] useful for therapy of epilepsyin WO 00/07988 but their connection with AMPA receptor and kainatereceptor has not been known at all.

As such, there has been a brisk demand for the compounds which inhibitAMPA receptor/kainate receptor and are useful as pharmaceutical agents.However, the compounds which exhibit an excellent inhibiting action toAMPA receptor and/or kainate receptor and are highly useful aspharmaceutical agents effectively acting in clinical field have not beenfound yet. Thus, an object of the present invention is to investigateand find a compound which inhibits AMPA receptor and/or kainate receptorwhich suppresses the neurotoxicity of excitatory neurotransmitters andachieves an excellent neuroprotective action as pharmaceutical agentsbeing useful as therapeutic/preventing/improving agents for variousnerve diseases.

DISCLOSURE OF THE INVENTION

Under such circumstances, the present inventors have carried out anintensive study and, as a result, they have succeeded in synthesizing anovel compound represented by the formula (I), a salt thereof orhydrates thereof, and have found an excellent method for producing thecompound or a salt thereof, and useful intermediate in the method.Further, quite surprisingly, they have found that the above compound(I), a salt or hydrates thereof shows an excellent antagonistic actionto AMPA receptor, whereupon the present invention has been accomplished.

A compound represented by the following formula, a salt thereof orhydrates thereof.

In the formula, Q indicates NH, O or S; and R¹, R², R³, R⁴ and R⁵ arethe same as or different from each other and each indicates hydrogenatom, a halogen atom, a C₁₋₆ alkyl group or a group represented by theformula —X-A (wherein X indicates a single bond, an optionallysubstituted C₁₋₆ alkylene group an optionally substituted C₂₋₆alkenylene group, an optionally substituted C₂₋₆ alkynylene group, —O—,—S—, —CO—, —SO—, —SO₂—, —N(R⁶)—, —N(R⁷)—CO—, —CO—N(R⁸)—, —N(R⁹)—CH₂—,—CH₂—N(R¹⁰)—, —CH₂—CO—, —CO—CH₂—, —N(R¹¹)—S(O)_(m)—, —S(O)_(n)—N(R¹²)—,—CH₂—S(O)_(p)—, —S(O)_(q)—CH₂—, —CH₂—O—, —O—CH₂—, —N(R¹³)—CO—N(R¹⁴)— or—N(R¹⁵)—CS—N(R¹⁶)— (wherein R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵and R¹⁶ indicate hydrogen atom, a C₁₋₆ alkyl group or a C₁₋₆ alkoxygroup; and m, n, p and q indicates an integer of 0, 1 or 2independently); and A indicates a C₃₋₈ cycloalkyl group, a C₃₋₈cycloalkenyl group, a 5 to 14 membered non-aromatic heterocyclic group,a C₆₋₁₄ aromatic hydrocarbocyclic group, or a 5 to 14 membered aromaticheterocyclic group which may be substituted respectively, provided that3 groups among R¹, R², R³, R⁴ and R⁵ are always the same as or differentfrom each other and each indicates —X-A; and the residual 2 groupsalways indicate hydrogen atom, a halogen atom or a C₁₋₆ alkyl group),provided that in the above-mentioned definition, the cases where (1) Qis O; R¹ and R⁵ are hydrogen atoms; and R², R³ and R⁴ are phenyl groups,(2) Q is O; R¹ and R⁴ are hydrogen atoms; and R², R³ and R⁵ are phenylgroups, and (3) Q is O; R¹ and R² are hydrogen atoms; and R³, R⁴ and R⁵are phenyl groups, are excluded.

That is, the present invention relates to (1) the compound representedby the above formula (I), a salt thereof or hydrates thereof; (2) thecompound according to the above (1), a salt thereof or hydrates thereof,which is represented by the formula:

wherein Q indicates NH, O or S; X¹, X² and X³ are the same as ordifferent from each other and each indicates a single bond, anoptionally substituted C₁₋₆ alkylene group, an optionally substitutedC₂₋₆ alkenylene group, an optionally substituted C₂₋₆ alkynylene group,—O—, —S—, —CO—, —SO—, —SO₂—, —N(R⁶)—, —N(R⁷)—CO—, —CO—N(R⁸)—,—N(R⁹)—CH₂—, —CH₂—N(R¹⁰)—, —CH₂—CO—, —CO—CH₂—, —N(R¹¹)—S(O)_(m)—,—S(O)_(n)—N(R¹²)—, —CH₂—S(O)_(p)—, —S(O)_(q)—CH₂—, —CH₂—O—, —O—CH₂—,—N(R¹³)—CO—N(R¹⁴)— or —N(R¹⁵)—CS—N(R¹⁶)— (wherein R⁶, R⁷, R⁸, R⁹, R¹⁰,R¹¹, R¹², R¹³, R¹⁴, R¹⁵ and R¹⁶ indicate hydrogen atom, a C₁₋₆ alkylgroup or a C₁₋₆ alkoxy group; and m, n, p and q are independent of eachother and each indicates an integer of 0, 1 or 2); A¹, A² and A³ are thesame as or different from each other and each indicates an optionallysubstituted C₃₋₈ cycloalkyl group, C₃₋₈ cycloalkenyl group, 5 to14-membered non-aromatic heterocyclic group, C₆₋₁₄ aromatichydrocarbocyclic group or 5 to 14-membered aromatic heterocyclic group;and R¹⁷ and R¹⁸ are the same as or different from each other and eachindicates hydrogen atom, a halogen atom or a C₁₋₆ alkyl group; (3) thecompound according to the above (2), a salt thereof or hydrates thereof,wherein X¹, X² and X³ are (1) single bond, (2) a C₁₋₆ alkylene group, aC₂₋₆ alkenylene group or a C₂₋₆ alkynylene group which may be optionallysubstituted respectively with one or more groups selected from thefollowing substituent group a, (3) —O—, (4) —S—, (5) —CO—, (6) —SO—, (7)—SO₂—, (8) —N(R⁶)—, (9) —N(R⁷)—CO—, (10) —CO—N(R⁸)—, (11) —N(R⁹)—CH₂—,(12) —CH₂—N(R¹⁰)—, (13) —CH₂—CO—, (14) —CO—CH₂—, (15) —N(R¹¹)—S(O)_(m)—,(16) —S(O)_(n)—N(R¹²)—, (17) —CH₂—S(O)_(p)—, (18) —S(O)_(q)—CH₂—, (19)—CH₂—O—, (20) —O—CH₂—, (21) —N(R¹³)—CO—N(R¹⁴)— or (22)—N(R¹⁵)—CS—N(R¹⁶)— (wherein R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵and R¹⁶, m, n, p and q have the same meanings as defined in the aboveclaim 1); and A¹, A² and A³ are a C₃₋₈ cycloalkyl group, a C₃₋₈cycloalkenyl group, a 5- to 14-membered non-aromatic heterocyclic group,a C₆₋₁₄ aromatic hydrocarbocyclic group or a 5- to 14-membered aromaticheterocyclic group which may be optionally substituted with one or moregroups selected from the following substituent group b (the substituentgroup a: the group consisting of hydroxy group, a halogen atom andnitrile group; and the substituent group b: the group consisting of (1)hydroxy group, (2) a halogen atom, (3) nitrile group, (4) nitro group,(5) a C₁₋₆ alkyl group, a C₂₋₆ alkenyl group or a C₂₋₆ alkynyl groupwhich may be optionally substituted respectively with one or more groupsselected from the group consisting of hydroxy group, nitrile group, ahalogen atom, a C₁₋₆ alkylamino group, a di-(C₁₋₆ alkyl) amino group, aC₂₋₆ alkenylamino group, a di(C₂₋₆ alkenylamino) group, a C₂₋₆alkynylamino group, a di(C₂₋₆ alkynylamino) group, an N—C₁₋₆alkyl-N—C₂₋₆ alkenylamino group, an N—C₁₋₆ alkyl-N—C₂₋₆ alkynylaminogroup, an N—C₂₋₆ alkenyl-N—C₂₋₆ alkynylamino group, an aralkyloxy group,a TBDMS oxy group, a C₁₋₆ alkylsulfonylamino group, a C₁₋₆alkylcarbonyloxy group, a C₂₋₆ alkenylcarbonyloxy group, a C₂₋₆alkynylcarbonyloxy group, an N—C₁₋₆ alkylcarbamoyl group, an N—C₂₋₆alkenylcarbamoyl group and an N—C₁₋₆ alkynylcarbamoyl group, (6) a C₁₋₆alkoxy group, a C₂₋₆ alkenyloxy group or a C₂₋₆ alkynyloxy group whichmay be optionally substituted respectively with one or more groupsselected from the group consisting of a C₁₋₆ alkylamino group, anaralkyloxy group and hydroxy group, (7) a C₁₋₆ alkylthio group, a C₂₋₆alkenylthio group or a C₂₋₆ alkynylthio group which may be optionallysubstituted respectively with one or more groups selected from the groupconsisting of hydroxy group, nitrile group, a halogen atom, a C₁₋₆alkylamino group, an aralkyloxy group, a TBDMS oxy group, a C₁₋₆alkylsulfonylamino group, a C₁₋₆ alkylcarbonyloxy group and a C₁₋₆alkylcarbamoyl group, (8) a carbonyl group substituted with a groupselected from the group consisting of a C₁₋₆ alkoxy group, amino group,a C₁₋₆ alkylamino group, a di(C₁₋₆ alkyl) amino group, a C₂₋₆alkenylamino group, a di(C₂₋₆ alkenyl) amino group, a C₂₋₆ alkynylaminogroup, a di(C₂₋₆ alkynyl) amino group, an N—C₁₋₆ alkyl-N—C₂₋₆alkenylamino group, an N—C₁₋₆ alkyl-N—C₂₋₆ alkynylamino group and anN—C₂₋₆ alkenyl-N—C₂₋₆ alkynylamino group, (9) amino group which may beoptionally substituted with one or two groups selected from the groupconsisting of a C₁₋₆ alkyl group, a C₂₋₆ alkenyl group, a C₂₋₆ alkynylgroup, a C₁₋₆ alkylsulfonyl group, a C₂₋₆ alkenylsulfonyl group, a C₂₋₆alkynylsulfonyl group, a C₁₋₆ alkylcarbonyl group, a C₂₋₆alkenylcarbonyl group and a C₂₋₆ alkynylcarbonyl group, (10) a C₁₋₆alkylsulfonyl group, (11) a C₂₋₆ alkenylsulfonyl group, (12) a C₂₋₆alkynylsulfonyl group, (13) a C₁₋₆ alkylsulfinyl group, (14) a C₂₋₆alkenylsulfinyl group, (15) a C₂₋₆ alkynylsulfinyl group, (16) a formylgroup, (17) a C₃₋₈ cycloalkyl group or a C₃₋₈ cycloalkenyl group whichmay be optionally substituted respectively with one or more groupsselected from the group consisting of hydroxy group, a halogen atom,nitrile group, a C₁₋₆ alkyl group, a C₁₋₆ alkyloxy group, a C₁₋₆alkyloxy C₁₋₆ alkyl group and an aralkyl group, (18) a 5- to 14-memberednon-aromatic heterocyclic group which may be optionally substituted withone or more groups selected from the group consisting of hydroxy group,a halogen atom, nitrile group, a C₁₋₆ alkyl group, a C₁₋₆ alkyloxygroup, a C₁₋₆ alkyloxy C₁₋₆ alkyl group and an aralkyl group, (19) aC₆₋₁₄ aromatic hydrocarbocyclic group which may be optionallysubstituted with one or more groups selected from the group consistingof hydroxy group, a halogen atom, nitrile group, a C₁₋₆ alkyl group, aC₁₋₆ alkyloxy group, a C₁₋₆ alkyloxy C₁₋₆ alkyl group and an aralkylgroup, and (20) a 5- to 14-membered aromatic heterocyclic group whichmay be optionally substituted with one or more groups selected from thegroup consisting of hydroxy group, a halogen atom, nitrile group, a C₁₋₆alkyl group, a C₁₋₆ alkyloxy group, a C₁₋₆ alkyloxy C₁₋₆ alkyl group andan aralkyl group); (4) the compound according to the above (2), a saltthereof or hydrates thereof, wherein A¹, A² and/or A³ are the same as ordifferent from each other and each is an optionally substituted C₃₋₈cycloalkyl, C₃₋₈ cycloalkenyl or 5- to 14-membered non-aromaticheteroring; (5) the compound according to the above (2), a salt thereofor hydrates thereof, wherein A¹, A² and/or A³ are the same as ordifferent from each other and each is an optionally substituted C₆₋₁₄aromatic hydrocarbon ring or a 5- to 14-membered aromatic heteroring;(6) the compound according to the above (2), a salt thereof or hydratesthereof, wherein A¹, A² and A³ are the same as or different from eachother and each represents phenyl group, pyrrolyl group, pyridyl group,pyridazinyl group, pyrimidinyl group, pyrazinyl group, thienyl group,thiazolyl group, furyl group, naphthyl group, quinolyl group,iso-quinolyl group, indolyl group, benzimidazolyl group, benzothiazolylgroup, benzoxazolyl group, imidazopyridyl group, carbazolyl group,cyclopentyl group, cyclohexyl group, cyclohexenyl group, dioxinyl group,adamantyl group, pyrrolidinyl group, piperidinyl group, piperazinylgroup or morpholyl group which may optionally have substituents,respectively; (7) the compound according to the above (2), a saltthereof or hydrates thereof, wherein A¹, A² and A³ are the same as ordifferent from each other and each is a group represented by theformula:

which may be substituted; (8) the compound according to the above (2), asalt thereof or hydrates thereof, wherein A¹, A² and A³ are the same asor different from each other and each is optionally substituted withhydroxyl group, a halogen atom, amino group or nitrile group; (9) thecompound according to the above (7), a salt thereof or hydrates thereof,wherein the substituents of A¹, A² and A³ are the same as or differentfrom each other and each is hydroxyl group, a halogen atom or, aminogroup, nitrile group or nitro group; (10) the compound according to theabove (1) or (2), a salt thereof or hydrates thereof, wherein Q isoxygen; (11) the compound according to the above (1) or (2), a saltthereof, hydrates thereof, wherein X¹, X² and X³ are the same as ordifferent from each other and each represents single bond, —CH₂—,—CH(OH)—, —CH₂—CH₂—, —CH═CH—, —C≡C—, —O— or —CO—; (12) the compoundaccording to the above (2), a salt thereof or hydrates thereof, whereinX¹, X² and X³ are single bonds; (13) the compound according to the above(2), a salt thereof or hydrates thereof, wherein R¹⁷ and R¹⁸ are thesame as or different from each other and each represents hydrogen atom,fluorine, chlorine, bromine, iodine, methyl group, ethyl group, n-propylgroup or iso-propyl group; (14) the compound according to the above (2),a salt thereof or hydrates thereof, wherein R¹⁷ and R¹⁸ representhydrogen atom; (15) the compound according to the above (1) or (2), asalt thereof or hydrates thereof, which is represented by the formula:

wherein X¹, X², X³, A¹, A², A³, R¹⁷ and R¹⁸ have the same meanings asdefined in the above (2); (16) the compound according to the above (15),a salt thereof or hydrates thereof, wherein A¹, A² and A³ are same as ordifferent from each other and each represents optionally substitutedC₆₋₁₄ aromatic hydrocarbon ring or 5- to 14-membered aromaticheteroring; (16) the compound according to the above (15), a saltthereof or hydrates thereof, wherein A¹, A² and A³ are same as ordifferent from each other and each represents optionally substitutedC₆₋₁₄ aromatic hydrocarbon ring or 5- to 14-membered aromaticheteroring; (17) the compound according to the above (15), a saltthereof or hydrates thereof, wherein A¹, A² and A³ are the same as ordifferent from each other and each represents optionally substitutedphenyl group, pyrrolyl group, pyridyl group, pyridazinyl group,pyrimidinyl group, pyrazinyl group, thienyl group, thiazolyl group,furyl group, naphthyl group, quinolyl group, iso-quinolyl group, indolylgroup, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group,imidazopyridyl group, carbazolyl group, cyclopentyl group, cyclohexylgroup, cyclohexenyl group, dioxinyl group, adamantyl group, pyrrolidinylgroup, piperidinyl group, piperazinyl group or morpholyl group; (18) thecompound according to the above (15), a salt thereof or hydratesthereof, wherein A¹, A² and A³ are the same as or different from eachother and each represents a group represented by the following formula:

which may be substituted; (19) the compound according to the above (15),a salt thereof or hydrates thereof, wherein the bonding site of thesubstituent at A¹, A² and/or A³ are α-position of the carbon atombonding to the group X¹, X² and X³, respectively; (20) the compoundaccording to the above (15), a salt thereof or hydrates thereof, whereinX¹, X² and X³ are single bonds; (21) the compound according to the above(15), a salt thereof or hydrates thereof, wherein R¹⁷ and R¹⁸ arehydrogen atoms; (22) the compound according to the above (1), a saltthereof or hydrates thereof, which is any one of compounds selectedfrom:

-   3-(2-cyanophenyl)-5-(2-methylsulfonylaminophenyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-chloro-3-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-nitrophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-aminophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-methylsulfonylaminophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-methylaminophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-dimethylaminophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-[3-(5-methoxymethyl-2-oxazolidinon-3-yl)-phenyl]-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-methoxycarbonylphenyl)    -1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-methylaminocarbonylphenyl)    -1,2-dihydropyridin-2-one;-   3-(2-cyano-3-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-(4-hydroxyphenyl)-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-(4-dimethylaminoethoxyphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-formylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-hydroxymethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-cyanomethylphenyl)-1,2-dihydropyridine-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-acetylaminomethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-methylsulfonylaminomethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-acetoxymethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-methylthiophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-methylsulfonylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-formylthiophen-3-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-diethylaminomethylthiophen-3-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-hydroxymethylthiophen-3-yl)-1-phenyl-1,2-dihydropyridine-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-benzyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1,5-diphenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-methoxyphenyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(3,4-dimethoxyphenyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(thiophen-3-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-fluorophenyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(thiophen-2-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(3-furfuryl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-furfuryl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-on,-   3-(2-methoxycarbonylphenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-phenyl-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-fluorophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-(3-methoxyphenyl)-1,2-dihydropyridin-2-one;-   3-(2-fluoro-3-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(4-methoxy-3-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-fluoro-3-pyridyl)-5-(2-pyridyl)-1-(3-methoxyphenyl)-1,2-dihydropyridin-2-one;-   3-(2-fluoro-3-pyridyl)-5-(2-pyridyl)-1-(3-fluorophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-fluorophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-fluorophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-methoxyphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-methoxyphenyl)-1,2-dihydropyridin-2-one;-   3-phenyl-5-(2-pyridyl)-1-(3-fluorophenyl)-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-(4-fluorophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-formylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-formylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-chlorophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-tolyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-trifluoromethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(thiophen-3-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-furfuryl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-tolyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-trifluoromethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-methoxypyridin-5-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(pyrimidin-5-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-benzyloxymethylpyridin-5-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-ethylthiopyridin-5-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-methoxypyridin-5-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-chloropyridin-5-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-fluoropyridin-5-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-methoxyphenyl)-1,2-dihydropyridin-2-one;-   3-phenyl-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one;-   3-(thiophen-3-yl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2,6-dimethylphenyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanothiophen-3-yl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-fluoro-3-pyridyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-(3-hydroxyphenyl)-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-(3-dimethylaminoethoxyphenyl)-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-(3-dimethylaminopropoxyphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-hydroxymethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-cyanomethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-cyanomethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(6-diethylaminomethyl-2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-phenyl-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one;-   3-(2-hydroxypyridin-6-yl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   1-(2-aminobenzothiazol-6-yl)-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(1-benzyl-1,2,3,6-tetrahydropyridin-5-yl)-1,2-dihydropyridin-2-one;-   3-[2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(6-methylpyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(5-methylpyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(3-hydroxypyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-phenyl-5-(2-thiazolyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-methoxypyridin-6-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   1-(4-aminophenyl)-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   1-(3-aminophenyl)-3-(2-cyanophenyl)-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-aminotoluen-4-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-[3-(dimethylaminoethoxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-[3-(piperidinoethoxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-[3-(pyrrolidinoethoxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-[3-(diisoproylaminoethoxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-[3-(4-piperidinobutyl-1-oxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-(4-nitrophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   1-phenyl-5-(2-pyridyl)-3-(2-thiazolyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-(3-pyridyl)-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one;-   3-(2-fluoropyridin-3-yl)-1-phenyl-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanopyridin-3-yl)-1-phenyl-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-(3-nitrophenyl)-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one;-   3-(2-nitrophenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-formylthiophen-3-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-naphthyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(1-naphthyl)-1,2-dihydropyridin-2-one;-   5-(2-aminopyridin-6-yl)-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one;-   5-(2-bromopyridin-6-yl)-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-morphorinopyridin-6-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-(3-hydroxyphenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-[3-(4-piperidyloxy)]phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   1-[3-(N-acetylpiperidin-4-yl-oxy)phenyl]-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-{3-[1-(methanesulfonyl)piperidin-4-yl-oxy]phenyl}-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   1-[3-(N-methylpiperidin-4-yl-oxy)phenyl]-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(6-chloro-1H-benzimidazol-2-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-nitrotoluen-4-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanothiophen-3-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-[2-(5-oxazolyl)phenyl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-[2-(5-oxazolyl)thiophen-3-yl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one;    and-   3-(2-ethoxycarbonylvinylthiophen-3-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one; (23)    a process for producing a compound represented by the formula:

(wherein, each A^(1a) and A^(3a) has the same meaning as defined below;and W represents a halogen atom) or a salt thereof, which comprisessubjecting the compound represented by the formula:

(wherein A^(1a) and A^(3a) are the same as or different from each otherand each indicates an optionally substituted C₆₋₁₄ aromatichydrocarbocyclic group or 5 to 14-membered aromatic heterocyclic group)or a salt thereof to a halogenation reaction; (24) a process forproducing a compound represented by the formula:

(wherein A^(1a) and A^(3a) have the same meanings as defined above) or asalt thereof, which comprises subjecting the compound represented by theformula:

(wherein A^(3a) has the same meaning as defined above) or a salt thereofand a boronic acid derivative represented by the formula A^(1a)B(OH)₂(wherein A^(1a) represents an optionally substituted C₆₋₁₄ aromatichydrocarbon ring or 5- to 14-membered aromatic heteroring) to a couplingreaction in the presence of a copper compound; (25) the productionprocess according to the above (24), which comprises subjecting thecompound represented by the above formula (VIII) or a salt thereofproduced by subjecting the compound represented by the formula:

(wherein A^(3a) has the same meaning as defined above; and Z³ indicatesa protecting group of an alcoholic hydroxy group) to de-protectingreaction and a boronic acid derivative represented by the formulaA^(1a)B(OH)₂ (wherein A^(1a) has the same meaning as defined above) to acoupling reaction in the presence of a copper compound; (26) theproduction process according to the above (24), which comprisesproducing the compound represented by the above formula (VIII) or a saltthereof by subjecting the compound represented by the above formula (IX)or a salt thereof produced by subjecting a boronic acid derivativerepresented by the formula:

(wherein Z³ has the same meaning as defined above) or a salt thereof andthe compound represented by the formula A^(3a)-Z¹ (wherein A^(3a) hasthe same meaning as defined above; and Z¹ represents a halogen atom) ora salt thereof to a coupling reaction in the presence of a palladiumcatalyst, to a de-protecting reaction; and then subjecting the compound(VIII) or a salt thereof and a boronic acid derivative represented bythe formula A^(1a)B(OH)₂ (wherein A^(1a) has the same meaning as definedabove) to a coupling reaction in the presence of a copper compound; (27)the production process according to the above (24), which comprisesproducing the compound represented by the above formula (X) or a saltthereof by reacting the compound represented by the formula:

(wherein Z³ has the same meaning as defined above; and W′ represents ahalogen atom) or a salt thereof and trimethoxyborane in the presence ofa base; producing the compound represented by the above formula (IX) ora salt thereof by subjecting the compound (X) or a salt and the compoundrepresented by the formula A^(3a)-Z¹ (wherein A^(3a) and Z¹ have thesame meanings as defined above) or a salt thereof to a coupling reactionin the presence of a palladium catalyst; producing the compoundrepresented by the above formula (VIII) or a salt thereof by subjectingthe compound (IX) or a salt thereof to a de-protecting reaction; andthen subjecting the compound (VIII) and a boronic acid derivativerepresented by the formula A^(1a)B(OH)₂ (wherein A^(1a) has the samemeaning as defined above) to a coupling reaction in the presence of acopper compound; (28) the production process according to the above(24), which comprises producing the compound represented by the aboveformula (X) or a salt thereof by reacting the compound represented bythe above formula (XI) or a salt thereof produced by reacting thecompound represented by the formula:

(wherein W′ and W″ are the same as or different from each other and eachrepresents halogen atoms) or a salt thereof and the compound representedby the formula Z³OM (wherein Z³ has the same meaning as defined above;and M represents an alkali metal atom) and trimethoxyborane in thepresence of a base; producing the compound represented by the aboveformula (IX) or a salt thereof by subjecting the compound (X) or a saltthereof and the compound represented by the formula A^(3a)-Z¹ (whereinA^(3a) and Z¹ have the same meanings as defined above) or a salt thereofto a coupling reaction in the presence of a palladium catalyst;producing the compound represented by the above formula (VIII) or a saltthereof by subjecting the compound (IX) or a salt thereof to ade-protecting reaction; and then subjecting the compound (VIII) and aboronic acid derivative represented by the formula A^(1a)B(OH)₂ (whereinA^(1a) has the same meaning as defined above) to a coupling reaction inthe presence of a copper compound; (29) the production process accordingto the above (23), which comprises subjecting the compound representedby the above formula (VI) and produced by the production processaccording to any of the above (24) to (28) or a salt thereof to ahalogenation reaction; (30) the production process according to theabove (23) or (29), wherein W is bromine or iodine; (31) the productionprocess according to the above (23) or (29), wherein the halogenationreaction for producing the compound (VII) or a salt thereof is (1) abromination reaction using N-bromosuccinimide or acetic acid-bromine or(2) an iodination reaction using N-iodosuccinimide or iodine; (32) theproduction process according to the above (23) or (29), wherein thehalogenation reaction for producing the compound (VII) or a salt thereofis carried out using N,N-dimethylformamide as a solvent; (33) theproduction process according to the above (23) or (29), wherein A^(1a)and A^(3a) are the same as or different from each other and eachrepresents an optionally substituted phenyl group, pyridyl group,pyridazinyl group, pyrimidinyl group, pyrazyl group, thienyl group,thiazolyl group, furyl group, naphthyl group, quinolyl group,iso-quinolyl group, indolyl group, benzimidazolyl group, benzothiazolylgroup, benzoxazolyl group, imidazopyridyl group or carbazolyl group;(34) the production process according to any of the above (24) to (28),wherein A^(1a) and A^(3a) are the same as or different from each otherand each represents an optionally substituted phenyl group, pyridylgroup, pyridazinyl group, pyrimidinyl group, pyrazinyl group, thienylgroup, thiazolyl group, furyl group, naphthyl group, quinolyl group,iso-quinolyl group, indolyl group, benzimidazolyl group, benzothiazolylgroup, benzoxazolyl group, imidazopyridyl group or carbazolyl group;(35) the production process according to any of the above (24) to (29),wherein the copper compound used for a coupling reaction using thecompound (VIII) or a salt thereof is copper acetate ordi-μ-hydroxo-bis[(N,N,N′,N′-tetramethylethylenediamine)copper(II)]chloride; (36) the production process according to any of the above(24) to (29), wherein the coupling reaction using the compound (VIII) ora salt thereof is carried out in the presence of a base; (37) theproduction process according to the above (36), wherein the base istriethylamine, pyridine or tetramethylethylenediamine; (38) theproduction process according to any of the above (24) to (29), whereinthe coupling reaction using the compound (VIII) or a salt thereof iscarried out using N,N-dimethylformamide as a solvent; (39) theproduction process according to any of the above (25) to (29), whereinZ³ is a C₁₋₆ alkyl group or a C₁₋₆ aralkyl group; (40) the productionprocess according to the above (25) to (29), wherein the reaction ofde-protection of the compound (IX) or a salt thereof is carried out inthe presence of an acid; (41) the production process according to theabove (40), wherein the acid is hydrochloric acid; (42) the productionprocess according to the above (26) to (29), wherein a catalyst in thecoupling reaction using the compound (X) or a salt thereof is palladiumacetate and triphenylphosphine; (43) the production process according tothe above (26) to (29), wherein the coupling reaction using the compound(X) or a salt thereof is carried out in the presence of a base; (44) theproduction process according to the above (43), wherein the base iscesium carbonate, sodium carbonate or potassium carbonate; (45) theproduction process according to any of the above (27) to (29), whereinW′ is bromine; (46) the production process according to the above (27)to (29), wherein the base used for the reaction of the compound (XI) ora salt thereof with trimethoxyborane is n-butyllithium; (47) theproduction process according to the above (28) or (29), wherein W′ andW″ are bromine; (48) the production process according to the above (28)or (29), wherein the compound represented by the formula Z³OM is sodiummethoxide or sodium ethoxide; (49) a process for producing a compoundrepresented by the formula:

(wherein, the ring D and the ring E have the same meanings as definedbelow; and W has the same meaning as defined above) or a salt thereof,which comprises subjecting a compound represented by the formula:

(wherein, the ring D ring indicates an optionally substituted pyridinering; and the ring E represents an optionally substituted benzene ring)or a salt thereof to a halogenation reaction; (50) a process forproducing a compound represented by the formula:

(wherein, the ring D and the ring E have the same meanings as definedabove) or a salt thereof, which comprises subjecting the compoundrepresented by the formula:

(wherein the ring D has the same meaning as defined above) or a saltthereof and a boronic acid derivative represented by the formulaPhB(OH)₂ (wherein Ph indicates an optionally substituted phenyl group)to a coupling reaction in the presence of a copper compound; (51) theproduction process according to the above (50), which comprisessubjecting the compound represented by the above formula (VIII)′ or asalt thereof produced by subjecting the compound represented by theformula:

(wherein the ring B and Z³ have the same meanings as defined above) or asalt thereof to a de-protecting reaction, and a boronic acid derivativerepresented by the formula PhB(OH)₂ (wherein Ph has the same meaning asdefined above) to a coupling reaction in the presence of a coppercompound; (52) the production process according to the above (50), whichcomprises producing the compound represented by the above formula (VII)′or a salt thereof by subjecting the compound represented by the aboveformula (IX)′ or a salt thereof produced by subjecting a boronic acidderivative represented by the formula:

(wherein Z³ has the same meaning as defined above) or a salt thereof andan optionally substituted 2-halogenopyridine or a salt thereof to acoupling reaction in the presence of a palladium catalyst to ade-protecting reaction; and then subjecting the compound (VIII)′ or asalt thereof and a boronic acid derivative represented by the formulaPhB(OH)₂ (wherein Ph has the same meaning as defined above) to acoupling reaction in the presence of a copper compound; (53) theproduction process according to the above (50), which comprisesproducing the compound represented by the above formula (X) or a saltthereof by reacting the compound represented by the formula:

(wherein Z³ has the same meaning as defined above; and W′ represents ahalogen atom) or a salt thereof and trimethoxyborane in the presence ofa base; producing the compound represented by the above formula (IX)′ ora salt thereof by subjecting the compound (X) or a salt thereof and anoptionally substituted 2-halogenopyridine or a salt thereof to acoupling reaction in the presence of a palladium catalyst; producing thecompound represented by the above formula (VIII)′ or a salt thereof bysubjecting the compound (IX)′ or a salt to a de-protecting reaction; andthen subjecting the compound (VIII)′ and a boronic acid derivativerepresented by the formula PhB(OH)₂ (wherein Ph has the same meaning asdefined above) in the presence of a copper compound; (54) the productionprocess according to the above (50), which comprises producing thecompound represented by the above formula (X) or a salt thereof byreacting the compound represented by the above formula (XI) or a saltthereof produced by reacting the compound represented by the formula:

(wherein W′ and W″ are the same as or different from each other and eachrepresents halogen atoms) or a salt thereof and the compound representedby the formula Z³OM (wherein Z³ and M have the same meanings as definedabove), and tirmethoxyborane in the presence of a base; producing thecompound represented by the above formula (IX)′ or a salt thereof bysubjecting the compound (X) or a salt and an optionally substituted2-halogenopyridine or a salt thereof to a coupling reaction in thepresence of a palladium catalyst; producing the compound represented bythe above formula (VIII) or a salt thereof by subjecting the compound(IX)′ or a salt to a de-protecting reaction; and then subjecting thecompound (VIII)′ and a boronic acid derivative represented by theformula PhB(OH)₂ (wherein Ph has the same meaning as defined above) to acoupling reaction in the presence of a copper compound; (55) theproduction process according to the above (25), which comprisessubjecting the compound represented by the above formula (VI)′ andproduced by the production process according to any of the above (29) to(32) or a salt thereof to a halogenation reaction; (56) the productionprocess according to the above (49) or (55), wherein W is bromine oriodine; (57) the production process according to the above (49) or (55),wherein the halogenation reaction for producing the compound (VII) or asalt thereof is (1) a bromination reaction using N-bromosuccinimide oracetic acid-bromine, or (2) an iodination reaction usingN-iodosuccinimide or iodine; (58) the production process according tothe above (49) or (55), wherein the halogenation reaction for producingthe compound (VII) or a salt thereof is carried out usingN,N-dimethylformamide as a solvent; (59) the production processaccording to the above (49) or (55), wherein A^(1a) and A^(3a) are thesame as or different from each other and each represents an optionallysubstituted phenyl group, pyridyl group, pyridazinyl group, pyrimidinylgroup, pyrazinyl group, thienyl group, thiazolyl group, furyl group,naphthyl group, quinolyl group, iso-quinolyl group, indolyl group,benzimidazolyl group, benzothiazolyl group, benzoxazolyl group,imidazopyridyl group or carbazolyl group; (60) the production processaccording to any of the above (50) to (54), wherein A^(1a) and A^(3a)are the same as or different from each other and each represents anoptionally substituted phenyl group, pyridyl group, pyridazinyl group,pyrimidinyl group, pyrazinyl group, thienyl group, thiazolyl group,furyl group, naphthyl group, quinolyl group, iso-quinolyl group, indolylgroup, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group,imidazopyridyl group or carbazolyl group; (61) the production processaccording to any of the above (50) to (55), wherein the copper compoundused for the coupling reaction using the compound (VIII) or a saltthereof is copper acetate ordi-μ-hydroxo-bis[(N,N,N′,N′-tetramethylethylenediamine)copper(II)]chloride; (62) the production process according to any of the above(50) to (55), wherein the coupling reaction using the compound (VIII) ora salt thereof is carried out in the presence of a base; (63) theproduction process according to the above (62), wherein the base istriethylamine, pyridine or tetramethylethylenediamine; (64) theproduction process according to any of the above (50) to (55), whereinthe coupling reaction using the compound (VIII) or a salt thereof iscarried out using N,N-dimethylformamide as a solvent; (65) theproduction process according to any of the above (51) to (55), whereinZ³ is a C₁₋₆ alkyl group or an aralkyl group; (66) the productionprocess according to the above (51) to (55), wherein the de-protectionreaction of the compound (IX) or a salt thereof is carried out in thepresence of an acid; (67) the production process according to the above(66), wherein the acid is hydrochloric acid; (68) the production processaccording to the above (52) to (55), wherein a catalyst in the couplingreaction using the compound (X) or a salt thereof is palladium acetateand triphenylphosphine; (69) the production process according to theabove (52) to (55), wherein the coupling reaction using the compound (X)or a salt thereof is carried out in the presence of a base; (70) theproduction process according to the above (69), wherein the base iscesium carbonate, sodium carbonate or potassium carbonate; (71) theproduction process according to any of the above (53) to (55), whereinW′ is bromine; (72) the production process according to the above (53)to (55), wherein the base used for the reaction of the compound (XI) ora salt thereof with trimethoxyborane is n-butyllithium; (73) theproduction process according to the above (54) or (55), wherein W′ andW″ are bromine; (74) the production process according to the above (54)or (55), wherein the compound represented by the formula Z³OM is sodiummethoxide or sodium ethoxide; (75) the production process according toany of the above (52) to (55), wherein the optionally substituted2-halogenopyridine is an optionally substituted 2-bromopyridine; (76) acompound represented by the following formula or a salt thereof:

wherein A^(1a) and A^(3a) are the same as or different from each otherand each indicates an optionally substituted C₆₋₁₄ aromatichydrocarbocyclic group or 5 to 14-membered aromatic heterocyclic group;and R indicates hydrogen atom or a halogen atom; (77) the compoundaccording to the above (76) or a salt thereof, wherein A^(1a) and A^(3a)are the same as or different from each other and each represents anoptionally substituted phenyl group, pyridyl group, pyridazinyl group,pyrimidinyl group, pyrazinyl group, thienyl group, thiazolyl group,furyl group, naphthyl group, quinolyl group, iso-quinolyl group, indolylgroup, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group,imidazopyridyl group or carbazolyl group; (78) the compound according tothe above (76) or a salt thereof, wherein A^(1a) and A^(3a) are the sameas or different from each other and each represents an optionallysubstituted phenyl group, pyridyl group, pyrimidinyl group, thienylgroup or furyl group; (79) the compound according to the above (76) or asalt thereof, wherein R is hydrogen atom or bromine; (80) apharmaceutical composition comprising a compound represented by thefollowing formula, a salt thereof or hydrates thereof:

in the formula, Q indicates NH, O or S; and R¹, R², R³, R⁴ and R⁵ arethe same as or different from each other and each indicates hydrogenatom, a halogen atom, a C₁₋₆ alkyl group or the formula —X-A (wherein Xindicates a single bond, a C₁₋₆ alkylene group which may optionally havea substituent, a C₂₋₆ alkenylene group which may optionally have asubstituent, a C₂₋₆ alkynylene group which may optionally have asubstituent, —O—, —S—, —CO—, —SO—, —SO₂—, —N(R⁶)—, —N(R⁷)—CO—,—CO—N(R⁸)—, —N(R⁹)—CH₂—, —CH₂—N(R¹⁰)—, —CH₂—CO—, —CO—CH₂—,—N(R¹¹)—S(O)_(m)—, —S(O)_(n)—N(R¹²)—, —CH₂—S(O)_(p)—, —S(O)_(q)—CH₂—,—CH₂—O—, —O—CH₂—, —N(R¹³)—CO—N(R¹⁴)— or —N(R¹⁵)—CS—N(R¹⁶)— (wherein R⁶,R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵ and R¹⁶ indicates hydrogenatom, a C₁₋₆ alkyl group or a C₁₋₆ alkoxy group; and m, n, p and q areindependent of each other and each indicates an integer of 0, 1 or 2);and A indicates an optionally substituted C₃₋₈ cycloalkyl group, C₃₋₈cycloalkenyl group, 5- to 14-membered non-aromatic heterocyclic group,C₆₋₁₄ aromatic hydrocarbocyclic group or 5- to 14-membered aromaticheterocyclic group), provided that 3 groups among R¹, R², R³, R⁴ and R⁵are always the same as or different from each other and each indicates—X-A; and the residual 2 groups always indicate hydrogen atom, a halogenatom or a C₁₋₆ alkyl group; (81) the pharmaceutical compositionaccording to the above (80), wherein it is an inhibitor to anα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (hereinafter,referred to as “AMPA”) receptor and/or a kainate receptor; (82) thepharmaceutical composition according to the above (80), wherein it is aninhibitor to an AMPA receptor; (83) the pharmaceutical compositionaccording to the above (80), wherein it is an inhibitor to an kainatereceptor; (84) the pharmaceutical composition according to the above(80), which is a therapeutic or preventive agent for the diseases inwhich an AMPA receptor or a kainate receptor is participated; (85) thepharmaceutical composition according to the above (80), which is atherapeutic or preventive agent for the diseases in which a kainatereceptor is participated; (86) the pharmaceutical composition accordingto the above (80), which is a therapeutic or preventive agent for acuteneurodegenerative disease; (87) the pharmaceutical composition accordingto the above (80), which is a therapeutic or preventive agent forcerebrovascular disorders at acute stage, head injury, spinal cordinjury, neuropathies due to hypoxia or hypoglycemia; (88) thepharmaceutical composition according to the above (80), which is atherapeutic or preventive agent for chronic neurodegenerative disease;(89) the pharmaceutical composition according to the above (80), whichis a therapeutic or preventive agent for Alzheimer's disease,Parkinson's disease, Huntington's chorea, amyotrophic lateral sclerosisor spinocerebellar degeneration; (90) the pharmaceutical compositionaccording to the above (80), which is an agent for treating orpreventing epilepsy, hepatic encephalopathy, peripheral neuropathy,Parkinson's syndrome, spasticity, pain, neuralgia, schizophrenia,anxiety, drug abuse, nausea, emesis, dysuria, paropsia caused byglaucoma, paracusis caused by antibiotics or food poisoning; (91) thepharmaceutical composition according to the above (80), which is anagent for treating or preventing infectious encephalomyelitis,cerebrovascular senile dementia or dementia or neurosis caused bycerebrospinal meningitis; (92) the pharmaceutical composition accordingto the above (91), wherein the infectious encephalomyelitis is HIVencephalomyelitis; (93) the pharmaceutical composition according to theabove (80), which is an agent for treating or preventing demyelinatingdisease; (94) the pharmaceutical composition according to the above(93), wherein the demyelinating disease is encephalitis, acutedisseminated encephalomyelitis, multiple sclerosis, acutepolyradiculoneuritis, Guillain-Barre syndrome, chronic inflammatorydemyelinating polyneuropathy, Marchifava-Bignami disease, centralpontine myelinolysis, neuromyelitis optica, Devic disease, Balo disease,HIV myelopathy, HTLV myelopathy, progressive multifocalleukoencephalopathy or secondary demyelinating disease; (95) thepharmaceutical composition according to the above (94), wherein thesecondary demyelinating disease is CNS erythematodes, polyarteritisnodosa, Sjoegren's syndrome, sarcoidosis or isolated cerebralvasculitis; and the like.

The present invention provides a process for preventing or treatingdiseases in which AMPA receptor or kainate receptor is participated, bydosing a pharmacologically effective dose of the compound represented bythe formula (I), a salt thereof or hydrates thereof to a patient.

The present invention provides use of the compound represented by theformula (I), a salt thereof or hydrates thereof for producing atherapeutic or preventive agent for diseases in which AMPA receptor orkainate receptor is participated.

In the present invention, “the diseases in which AMPA receptor orkainate receptor is participated” include acute neurodegenerativedisease; cerebrovascular disorders at acute stage; head injury; spinalcord injury; and neuropathies due to hypoxia or hypoglycemia; chronicneurodegenerative disease; Alzheimer's disease; Parkinson s disease;Huntington's chorea; amyotrophic lateral sclerosis; spinocerebellardegeneration; epilepsy; hepatic encephalopathy; peripheral neuropathy;Parkinson's syndrome; spasticity; pain; neuralgia; schizophrenia;anxiety; drug abuse; nausea; emesis; dysuria; paropsia caused byglaucoma; paracusis caused by antibiotics; food poisoning; infectiousencephalomyelitis; cerebrovascular dementia; dementia or neurosis causedby meningitis; and demyelinating diseases.

DETAILED DESCRIPTION OF THE INVENTION

As hereunder, meanings of the symbols, terms, etc. mentioned in thespecification of this application will be explained, whereby the presentinvention will be illustrated in detail.

As “acute neurodegenerative disease” in the present invention, forexample, cerebrovascular disorders at acute stage (subarachnoidhemorrhage, cerebral infarction and the like), head injury, spinal cordinjury, and neuropathies due to hypoxia or hypoglycemia; and the likeare mentioned. As “chronic neurodegenerative disease”, for example,Alzheimer's disease, Parkinson's disease, Huntington's chorea,amyotrophic lateral sclerosis, spinocerebellar degeneration and the likeare mentioned. As “infectious encephalomyelitis”, for example, HIVencephalomyelitis is mentioned, and as “demyelinating disease”, forexample, encephalitis, acute disseminated encephalomyelitis, multiplesclerosis, acute polyradiculoneuritis, Guillain-Barre syndrome, chronicinflammatory demyelinating polyneuropathy, Marchifava-Bignami disease,central pontine myelinolysis, neuromyelitis optica, Devic disease, Balodisease, HIV myelopathy, HTLV myelopathy, progressive multifocalleukoencephalopathy, secondary demyelinating disease and the like arementioned. As “the secondary demyelinating disease” mentioned above, forexample, CNS lupus erythematodes, polyarteritis nodosa, Sjoegren'ssyndrome, sarcoidosis, isolated cerebral vasculitis and the like arementioned.

The term “and/or” used in the present invention is used in the meaningthat both cases in case of “and” and in case of “or” are included.

Incidentally, in the specification of this application, althoughstructural formula of a compound may express a certain isomer for thesake of convenience, the present invention covers all isomers such asgeometrical isomers resulted from the structure of the compound, opticalisomers due to asymmetric carbon, rotamers, stereo isomers and tautomersas well as a mixture of isomers and the present invention is not limitedto the description of the formula given for the sake of convenience butmay be another isomer or may be a mixture. Accordingly, although it ispossible that an asymmetric carbon atom is present in a molecule andaccordingly that optically active substance and racemic substance may bepresent, the present invention is not limited thereto but covers any ofthem. Further, crystal polymorphism may be present but, again, there isno limitation but any of single crystal form or a mixture will do. Thecompound (I) or its salt related to the present invention may be ananhydride or a hydrate, and either of them are included in the scope ofclaim for patent in the present invention. The metabolite which isgenerated by decomposing the compound (I) related to the presentinvention in vivo, and the prodrug of the compound (I) or its saltrelated to the present invention produce are also included in the scopeof claim for patent in the present invention.

The “halogen atom” used in the present invention indicates fluorine,chlorine, bromine, iodine and the like, and the preferable atom includefluorine, chlorine and bromine.

The “C₁₋₆ alkyl group” used in the present invention indicates an alkylgroup having 1 to 6 carbons, and examples include linear chain orbranched chain alkyl groups such as methyl group, ethyl group, n-propylgroup, iso-propyl group, n-butyl group, iso-butyl group, sec-butylgroup, tert-butyl group, n-pentyl group, 1,1-dimethylpropyl group,1,2-dimethylpropyl group, 2,2-dimethylpropyl group, 1-ethylpropyl group,2-ethylpropyl group, n-hexyl group, 1-methyl-2-ethylpropyl group,1-ethyl-2-methylpropyl group, 1,1,2-trimethylpropyl group,1-propylpropyl group, 1-methylbutyl group, 2-methylbutyl group,1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 2,2-dimethylbutylgroup, 1,3-dimethylbutyl group, 2,3-dimethylbutyl group, 2-ethylbutylgroup, 2-methylpentyl group, 3-methylpentyl group, and the like.

The “C₂₋₆ alkenyl group” used in the present invention indicates analkenyl group having 2 to 6 carbons, and examples of the preferablegroup include vinyl group, allyl group, 1-propenyl group, 2-propenylgroup, iso-propenyl group, 2-methyl-1-propenyl group,3-methyl-1-propenyl group, 2-methyl-2-propenyl group,3-methyl-2-propenyl group, 1-butenyl group, 2-butenyl group, 3-butenylgroup, 1-pentenyl group, 1-hexenyl group, 1,3-hexadienyl group,1,6-hexadienyl group, and the like.

The “C₂₋₆ alkynyl group” used in the present invention indicates analkynyl group having 2 to 6 carbons, and examples of the preferablegroup include ethynyl group, 1-propynyl group, 2-propynyl group,1-butynyl group, 2-butynyl group, 3-butynyl group, 3-methyl-1-propynylgroup, 1-ethynyl-2-propynyl group, 2-methyl-3-propynyl group, 1-pentynylgroup, 1-hexynyl group, 1,3-hexadiynyl group, 1,6-hexadiynyl group, andthe like.

The “C₁₋₆ alkoxy group” used in the present invention indicates analkoxy group having 1 to 6 carbons, and examples include methoxy group,ethoxy group, n-propoxy group, iso-propoxy group, sec-propoxy group,n-butoxy group, iso-butoxy group, sec-butoxy group, tert-butoxy group,n-pentyloxy group, iso-pentyloxy group, sec-pentyloxy group, n-hexoxygroup, iso-hexoxy group, 1,1-dimethylpropoxy group, 1,2-dimethylpropoxygroup, 2,2-dimethylpropoxy group, 2-ethylpropoxy group,1-methyl-2-ethylpropoxy group, 1-ethyl-2-methylpropoxy group,1,1,2-trimethylpropoxy group, 1,1,2-trimethylpropoxy group,1,1-dimethylbutoxy group, 1,2-dimethylbutoxy group, 2,2-dimethylbutoxygroup, 2,3-dimethylbutoxy group, 1,3-dimethylbutoxy group, 2-ethylbutoxygroup, 1,3-dimethylbutoxy group, 2-methylpentoxy group, 3-methylpentoxygroup, hexyloxy group, and the like.

The “C₂₋₆ alkenyloxy group” used in the present invention indicates analkenyloxy group having 2 to 6 carbons, and examples of the preferablegroup include vinyloxy group, allyloxy group, 1-propenyloxy group,2-propenyloxy group, iso-propenyloxy group, 2-methyl-1-propenyloxygroup, 3-methyl-1-propenyloxy group, 2-methyl-2-propenyloxy group,3-methyl-2-propenyloxy group, 1-butenyloxy group, 2-butenyloxy group,3-butenyloxy group, 1-pentenyloxy group, 1-hexenyloxy group,1,3-hexadienyloxy group, 1,6-hexadienyloxy group, and the like.

The “C₃₋₈ cycloalkyl group” used in the present invention indicates acycloalkyl group composed of 3 to 8 carbon atoms, and examples includecyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexylgroup, cycloheptyl group, cyclooctyl group, and the like.

The “C₃₋₈ cycloalkenyl group” used in the present invention indicates aC₃₋₈ cycloalkenyl group composed of 3 to 8 carbon atoms, and examplesinclude cyclopropen-1-yl, cyclopropen-3-yl, cyclobuten-1-yl,cyclobuten-3-yl, 1,3-cyclobutadien-1-yl, cyclopenten-1-yl,cyclopenten-3-yl, cyclopenten-4-yl, 1,3-cyclopentadien-1-yl,1,3-cyclopentadien-2-yl, 1,3-cyclopentadien-5-yl, cyclohexen-1-yl,cyclohexen-3-yl, cyclohexen-4-yl, 1,3-cyclohexadien-1-yl,1,3-cyclohexadien-2-yl, 1,3-cyclohexadien-5-yl, 1,4-cyclohexadien-3-yl,1,4-cyclohexadien-1-yl, cyclohepten-1-yl, cyclohepten-3-yl,cyclohepten-4-yl, cyclohepten-5-yl, 1,3-cyclohepten-2-yl,1,3-cyclohepten-1-yl, 1,3-cycloheptadien-5-yl, 1,3-cycloheptadien-6-yl,1,4-cycloheptadien-3-yl, 1,4-cycloheptadien-2-yl,1,4-cycloheptadien-1-yl, 1,4-cycloheptadien-6-yl,1,3,5-cycloheptatrien-3-yl, 1,3,5-cycloheptatrien-2-yl,1,3,5-cycloheptatrien-1-yl, 1,3,5-cycloheptatrien-7-yl, cycloocten-1-yl,cycloocten-3-yl, cycloocten-4-yl, cycloocten-5-yl,1,3-cyclooctadien-2-yl, 1,3-cyclooctadien-1-yl, 1,3-cyclooctadien-5-yl,1,3-cyclooctadien-6-yl, 1,4-cyclooctadien-3-yl, 1,4-cyclooctadien-2-yl,1,4-cyclooctadien-1-yl, 1,4-cyclooctadien-6-yl, 1,4-cyclooctadien-7-yl,1,5-cyclooctadien-3-yl, 1,5-cyclooctadien-2-yl,1,3,5-cyclooctatrien-3-yl, 1,3,5-cyclooctatrien-2-yl,1,3,5-cyclooctatrien-1-yl, 1,3,5-cyclooctatrien-7-yl,1,3,6-cyclooctatrien-2-yl, 1,3,6-cyclooctatrien-1-yl,1,3,6-cyclooctatrien-5-yl, 1,3,6-cyclooctatrien-6-yl group, and thelike.

The “5 to 14 membered non-aromatic heterocyclic group” used in thepresent invention means a mono-cyclic type, di-cyclic type, ortri-cyclic type 5 to 14 membered non-aromatic heterocyclic group whichcontains one or more of hetero atoms selected from a group whichconsists of nitrogen atom, sulfur atom and oxygen atom. Specificexamples in the group include, for example, pyrrolidinyl group, pyrrolylgroup, piperidinyl group, piperazinyl group, imidazolyl group,pyrazolidyl group, imidazolidyl group, morpholyl group, tetrahydrofurylgroup, tetrahydropyranyl group, pyrrolinyl group, dihydrofuryl group,dihydropyranyl group, imidazolinyl group, oxazolinyl group, and thelike. Further, a group derived from a pyridone ring and a non-aromaticcondensed ring (for example, a group derived from a phthalimide ring, asuccinimide ring, and the like) are also included in the non-aromaticheterocyclic group.

The “C₆₋₁₄ aromatic hydrocarbocyclic group” and the “aryl group” used inthe present invention mean an aromatic hydrocarbocyclic group havingwhich is composed of 6 to 14 carbon atoms, and a mono-cyclic group, anda condensed group of a di-cyclic group, a tri-cyclic group and the likeare also included. Specific examples in the group include phenyl group,indenyl group, 1-naphthyl group, 2-naphthyl group, azulenyl group,heptalenyl group, biphenyl group, indathenyl group, acenaphthyl group,fluorenyl group, phenalenyl group, phenanthrenyl group, anthracenylgroup, cyclopentacyclooctenyl group, benzocyclooctenyl group etc.

The “5 to 14 membered aromatic heterocyclic group” and the “heteroarylgroup” used in the present invention mean a mono-cyclic type, di-cyclictype, or tri-cyclic type 5 to 14 membered aromatic heterocyclic groupwhich contains one or more of hetero atoms selected from a group whichconsists of nitrogen atom, sulfur atom and oxygen atom. For example,specific examples in the group include 1) aromatic heterocyclic groupscontaining nitrogen such as pyrrolyl group, pyridyl group, pyridazinylgroup, pyrimidinyl group, pyrazinyl group, triazolyl group, tetrazolylgroup, benzotriazolyl group, pyrazolyl group, imidazolyl group,benzimidazolyl group, indolyl group, iso-indolyl group, indolizinylgroup, prenyl group, indazolyl group, quinolyl group, iso-quinolylgroup, quinoliziyl group, phthalazyl group, naphthylidinyl group,quinoxalyl group, quinazolinyl group, cynnolinyl group, pteridinylgroup, imidazotriazinyl group, pyrazinopyridazinyl group, acridinylgroup, phenanthridinyl group, carbazolyl group, carbazolinyl group,perimidinyl group, phenanthrolinyl group, phenacinyl group,imidazopyridinyl group, imidazopyrimidinyl group, pyrazolopyridinylgroup, pyrazolopyridinyl group etc; 2) aromatic heterocyclic groupscontaining sulfur such as thienyl group or benzothienyl group; 3)aromatic heterocyclic groups containing oxygen such as furyl group,pyranyl group, cyclopentapyranyl group, benzofuryl group oriso-benzofuryl group; and 4) aromatic heterocyclic groups containing 2or more of different hetero atoms such as thiazolyl group, iso-thiazolylgroup, benzothiazolyl group, benzthiadiazolyl group, phenothiazinylgroup, isoxazolyl group, furazanyl group, phenoxazinyl group, oxazolylgroup, isoxazoyl group, benzoxazolyl group, oxadiazolyl group,pyrazoloxadiazolyl group, imidazothiazolyl group, thienofuranyl group,furopyrrolyl group or pyridoxadinyl group.

The groups indicated by A, A¹, A² and A³ in the formula (I) in thepresent invention indicate independently an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₃₋₈ cycloalkenyl group, anoptionally substituted 5 to 14 membered non-aromatic heterocyclic group,an optionally substituted C₆₋₁₄ aromatic hydrocarbocyclic group or anoptionally substituted 5 to 14 membered aromatic heterocyclic group, andeach of the groups has the same meanings as the above definitions,respectively. The preferable group in A, A¹, A² and A³ is notspecifically limited, but the more preferable group includes phenylgroup, pyrrolyl group, pyridyl group, pyridazinyl group, pyrimidinylgroup, pyrazinyl group, thienyl group, thiazolyl group, furyl group,naphthyl group, quinolyl group, iso-quinolyl group, indolyl group,benzimidazolyl group, benzothiazolyl group, benzoxazolyl group,imidazopyridyl group, carbazolyl group, cyclopentyl group, cyclohexylgroup, cyclohexenyl group, dioxinyl group, adamantyl group, pyrrolidinylgroup, piperidinyl group, piperazinyl group and morpholinyl group whichmay be substituted, respectively, etc. The more preferable groupincludes a group represented by the formula:

which may optionally have substituents respectively, etc., and the mostpreferable group includes a group represented by the formula:

which may optionally have substituents respectively, etc.

Examples of the preferable group in the “substituents” of the groupsindicated by A, A¹, A² and A³ in the formula (I) include a group such ashydroxy group, a halogen atom, nitrile group, nitro group, a C₁₋₆ alkylgroup, C₂₋₆ alkenyl group, C₂₋₆ alkynyl group, C₁₋₆ alkoxy group, C₂₋₆alkenyloxy group, C₂₋₆ alkynyloxy group, C₁₋₆ alkylthio group, C₂₋₆alkenylthio group, C₂₋₆ alkynylthio group, amino group, a substitutedcarbonyl group, C₁₋₆ alkylsulfonyl group, C₂₋₆ alkenylsulfonyl group,C₂₋₆ alkynylsulfonyl group, C₁₋₆ alkylsulfinyl group, C₂₋₆alkenylsulfinyl group, C₂₋₆ alkynylsulfinyl group, formyl group, aralkylgroup, heteroarylalkyl group, aralkyloxy group, heteroarylalkyloxygroup, C₃₋₈ cycloalkyl group, C₃₋₈ cycloalkenyl group, 5 to 14 memberednon-aromatic heterocyclic group, C₆₋₁₄ aromatic hydrocarbon group, 5 to14 membered aromatic heterocyclic group etc., which may be substituted,respectively.

Examples of the preferable group in the “halogen atom” include fluorineatom, chlorine atom, bromine atom, iodine atom etc., and the morepreferable example includes fluorine atom, chlorine atom and bromineatom.

Examples of the preferable group in the “C₁₋₆ alkyl group which mayoptionally have substituents” include methyl group, ethyl group,n-propyl group, iso-propyl group, n-butyl group, iso-butyl group,tert-butyl group, n-pentyl group, iso-pentyl group, neopentyl group,n-hexyl group, 1-methylpropyl group, 1,2-dimethylpropyl group,2-ethylpropyl group, 1-methyl-2-ethylpropyl group,1-ethyl-2-methylpropyl group, 1,1,2-trimethylpropyl group, 1-methylbutylgroup, 2-methylbutyl group, 1,1-dimethylbutyl group, 2,2-dimethylbutylgroup, 2-ethylbutyl group, 1,3-dimethylbutyl group, 2-methylpentylgroup, 3-methylpentyl group etc. Examples of the preferable group in the“C₂₋₆ alkenyl group which may optionally have substituents” include avinyl group, allyl group, 1-propenyl group, iso-propenyl group,1-buten-1-yl group, 1-buten-2-yl group, 1-buten-3-yl group, 2-buten-1-ylgroup, 2-buten-2-yl group etc., which may be substituted, respectively.Examples of the preferable group in the “C₂₋₆ alkynyl group which mayoptionally have substituents respectively” include an ethynyl group,1-propynyl group, 2-propynyl group, butynyl group, pentynyl group,hexynyl group etc., which may be substituted, respectively. Further,preferable examples of the “substituents” in the “which may optionallyhave substituents” include 1 or more groups selected from hydroxy group,nitrile group, a halogen atom, an N—C₁₋₆ alkylamino group, anN,N-di-C₁₋₆ alkylamino group, an N—C₂₋₆ alkenylamino group, anN,N-di-C₂₋₆ alkenylamino group, an N—C₂₋₆ alkynylamino group, anN,N-di-C₂₋₆ alkynylamino group, a C₆₋₁₄ aromatic hydrocarbocyclic group(for example, phenyl group etc.), a 5 to 14 membered aromaticheterocyclic group (for example, thienyl group, furyl group, pyridylgroup, pyridazyl group, pyrimidinyl group, pyrazyl group etc.), anaralkyloxy group, a heteroaryloxy group, a TBDMS-oxy group, a C₁₋₆alkylsulfonylamino group, a C₂₋₆ alkenylsulfonylamino group, a C₂₋₆alkynylsulfonylamino group, a C₁₋₆ alkylcarbonyloxy group, a C₂₋₆alkenylcarbonyloxy group, a C₂₋₆ alkynylcarbonyloxy group, a C₁₋₆alkylcarbamoyl group, a C₂₋₆ alkenylcarbamoyl group, a C₂₋₆alkynylcarbamoyl group, and the like.

Preferable examples in the “C₁₋₆ alkoxy group which may optionally havesubstituents” include methoxy group, ethoxy group, n-propoxy group,iso-propoxy group, sec-propoxy group, n-butoxy group, iso-butoxy group,sec-butoxy group, tert-butoxy group, n-pentoxy group, iso-pentoxy group,sec-pentoxy group, tert-pentoxy group, n-hexoxy group, iso-hexoxy group,1,2-dimethylpropoxy group, 2-ethylpropoxy group, 1-methyl-2-ethylpropoxygroup, 1-ethyl-2-methylpropoxy group, 1,1,2-trimethylpropoxy group,1,1-dimethylbutoxy group, 2,2-dimethylbutoxy group, 2-ethylbutoxy group,1,3-dimethylbutoxy group, 2-methylpentoxy group, 3-methylpentoxy group,hexyloxy group etc. Preferable examples in the “C₂₋₆ alkenyloxy groupwhich may optionally have substituents” include vinyloxy group, allyloxygroup, 1-propenyloxy group, iso-propenyloxy group, 1-buten-1-yloxygroup, 1-buten-2-yloxy group, 1-buten-3-yloxy group, 2-buten-1-yloxygroup, 2-buten-2-yloxy group etc. Preferable examples in the “C₂₋₆alkynyloxy group which may optionally have substituents” includeethynyloxy group, 1-propynyloxy group, 2-propynyloxy group, butynyloxygroup, pentynyloxy group, hexynyloxy group etc. Further, preferableexamples of the “substituents” in the “which may optionally havesubstituents” include 1 or more groups selected from an C₁₋₆ alkylaminogroup, an aralkyloxy group, hydroxy group, and the like.

Respectively preferable examples in the “C₁₋₆ alkylthio group which mayoptionally have substituents”, “C₂₋₆ alkenylthio group which mayoptionally have substituents” and “C₂₋₆ alkynylthio group which mayoptionally have substituents” include a C₁₋₆ alkylthio group (forexample, methylthio group, ethylthio group, n-propylthio group,iso-propylthio group, n-butylthio group, iso-butylthio group,tert-butylthio group, n-pentylthio group, iso-pentylthio group,neopentylthio group, n-hexylthio group etc.), a C₂₋₆ alkenylthio group(for example, vinylthio group, allylthio group, 1-propenylthio group,iso-propenylthio group, 1-buten-1-ylthio group, 1-buten-2-ylthio group,1-buten-3-ylthio group, 2-buten-1-ylthio group, 2-buten-2-ylthio groupetc.) and a C₂₋₆ alkynylthio group (for example, ethynylthio group,1-propynylthio group, 2-propynylthio group, butynylthio group,pentynylthio group, hexynylthio group etc.), which may be optionallysubstituted by 1 or more groups selected from the group consisting ofhydroxy group, a halogen atom, nitrile group and nitro group.

Preferable examples in the “carbonyl group which was substituted”include a group which is represented by the formula —CO—W (examples of Win the formula include a C₁₋₆ alkyl group, a C₂₋₆ alkenyl group, a C₂₋₆alkynyl group, a C₁₋₆ alkoxy group, amino group, an N—C₁₋₆ alkylaminogroup, an N,N-di(C₁₋₆ alkyl) amino group, an N—C₂₋₆ alkenylamino group,an N,N-di(C₂₋₆ alkenyl) amino group, an N—C₂₋₆ alkynylamino group, anN,N-di(C₂₋₆ alkynyl) amino group, an N—C₁₋₆ alkyl-N—C₂₋₆ alkenylaminogroup, an N—C₁₋₆ alkyl-N—C₂₋₆ alkynylamino group, an N—C₂₋₆alkenyl-N—C₂₋₆ alkynylamino group etc.).

Examples of the “substituents” in the “amino group which may optionallyhave substituents” include 1 or 2 groups selected from a C₁₋₆ alkylgroup, C₂₋₆ alkenyl group, C₂₋₆ alkynyl group, C₁₋₆ alkylsulfonyl group,C₂₋₆ alkenylsulfonyl group, C₂₋₆ alkynylsulfonyl group, C₁₋₆alkylcarbonyl group, C₂₋₆ alkenylcarbonyl group, C₂₋₆ alkynylcarbonylgroup etc., which may be substituted, respectively. Preferable examplesin the “substituents” of the C₁₋₆ alkyl group, C₂₋₆ alkenyl group, C₂₋₆alkynyl group, C₁₋₆ alkylsulfonyl group, C₂₋₆ alkenylsulfonyl group,C₂₋₆ alkynylsulfonyl group, C₁₋₆ alkylcarbonyl group, C₂₋₆alkenylcarbonyl group and C₂₋₆ alkynylcarbonyl group include hydroxygroup, a halogen atom, nitrile group, a C₁₋₆ alkoxy group, a C₁₋₆alkylthio group etc. Specifically preferable examples in the “aminogroup which may optionally have substituents” in particular includemethylamino group, ethylamino group, n-propylamino group,iso-propylamino group, n-butylamino group, iso-butylamino group,tert-butylamino group, n-pentylamino group, iso-pentylamino group,neopentylamino group, n-hexylamino group, 1-methylpropylamino group,1,2-dimethylpropylamino group, 2-ethylpropylamino group,1-methyl-2-ethylpropylamino group, 1-ethyl-2-methylpropylamino group,1,1,2-trimethylpropylamino group, 1-methylbutylamino group,2-methylbutylamino group, 1,1-dimethylbutylamino group,2,2-dimethylbutylamino group, 2-ethylbutylamino group,1,3-dimethylbutylamino group, 2-methylpentylamino group,3-methylpentylamino group, N,N-dimethylamino group, N,N-diethylaminogroup, N,N-di(n-propyl)amino group, N,N-di(iso-propyl)amino group,N,N-di(n-butyl)amino group, N,N-di(iso-butyl) amino group,N,N-di(tert-butyl) amino group, N,N-di(n-pentyl)amino group,N,N-di(iso-pentyl)amino group, N,N-di(neopentyl)amino group,N,N-di(n-hexyl)amino group, N,N-di(1-methylpropyl)amino group,N,N-di(1,2-dimethylpropyl)amino group, N-methyl-N-ethylamino group,N-ethyl-N-(n-propyl)amino group, N-ethyl-N-(iso-propyl)amino group,vinylamino group, allylamino group, (1-propenyl)amino group,iso-propenylamino group, (1-buten-1-yl) amino group, (1-buten-2-yl)amino group, (1-buten-3-yl)amino group, (2-buten-1-yl)amino group,(2-buten-2-yl)amino group, N,N-divinylamino group, N,N-diallylaminogroup, N,N-di(1-propenyl)amino group, N,N-di(iso-propenyl) amino group,N-vinyl-N-allylamino group, ethynylamino group, 1-propynylamino group,2-propynylamino group, butynylamino group, pentynylamino group,hexynylamino group, N,N-diethynylamino group, N,N-di(1-propynyl)aminogroup, N,N-di(2-propynyl)amino group, N,N-dibutynylamino group,N,N-dipentynylamino group, N,N-dihexynylamino group, hydroxymethylaminogroup, 1-hydroxyethylamino group, 2-hydroxyethylamino group,3-hydroxy-n-propylamino group, methylsulfonylamino group,ethylsulfonylamino group, n-propylsulfonylamino group,iso-propylsulfonylamino group, n-butylsulfonylamino group,tert-butylsulfonylamino group, vinylsulfonylamino group,allylsulfonylamino group, iso-propenylsulfonylamino group,iso-pentenylsulfonylamino group, ethynylsulfonylamino group,methylcarbonylamino group, ethylcarbonylamino group,n-propylcarbonylamino group, iso-propylcarbonylamino group,n-butylcarbonylamino group, tert-butylcarbonylamino group,vinylcarbonylamino group, allylcarbonylamino group,iso-propenylcarbonylamino group, iso-pentenylcarbonylamino group,ethynylcarbonylamino group etc.

Respectively preferable examples in the “C₁₋₆ alkylsulfonyl group whichmay optionally have substituents”, “C₂₋₆ alkenylsulfonyl group which mayoptionally have substituents”, “C₂₋₆ alkynylsulfonyl group which mayoptionally have substituents”, “C₁₋₆ alkylsulfinyl group which mayoptionally have substituents”, “C₂₋₆ alkenylsulfinyl group which mayoptionally have substituents” and “C₂₋₆ alkynylsulfinyl group which mayoptionally have substituents” include methylsulfonyl group,ethylsulfonyl group, n-propylsulfonyl group, iso-propylsulfonyl group,n-butylsulfonyl group, tert-butylsulfonyl group, vinylsulfonyl group,allylsulfonyl group, iso-propenylsulfonyl group, iso-pentenylsulfonylgroup, ethynylsulfonyl group, methylsulfinyl group, ethylsulfinyl group,n-propylsulfinyl group, iso-propylsulfinyl group, n-butylsulfinyl group,tert-butylsulfinyl group, vinylsulfinyl group, allylsulfinyl group,iso-propenylsulfinyl group, iso-pentenylsulfinyl group, ethynylsulfinylgroup etc.

Preferable examples in the “aralkyl group” and “heteroarylalkyl group”include benzyl group, phenethyl group, naphthylmethyl group,naphthylethyl group, pyridylmethyl group, pyridylethyl group,thienylmethyl group, thienylethyl group etc., preferable examples in the“aralkyloxy group” include benzyloxy group, phenethyloxy group,phenylpropoxy group, naphthylmethyloxy group, naphthylethyloxy group,naphthylpropyloxy group etc., and preferable examples in the“heteroarylalkyloxy group” include pyridylmethyloxy group,pyrazinylmethyloxy group, pyrimidinylmethyloxy group, pyrrolylmethyloxygroup, imidazolylmethyloxy group, pyrazolylmethyloxy group,quinolylmethyloxy group, iso-quinolylmethyloxy group, fulfuryloxy group,thienylmethyloxy group, thiazolylmethyloxy group etc.

Preferable examples in the “C₃₋₈ cycloalkyl group which may optionallyhave substituents” and “C₃₋₈ cycloalkenyl group which may optionallyhave a substituent” include a C₃₋₈ cycloalkyl group (for example,cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexylgroup, cycloheptyl group, and the like) and a C₃₋₈ cycloalkenyl group(for example, cyclopropenyl group, cyclopropenyl group, cyclobutenylgroup, cyclopentenyl group, cyclohexenyl group, cycloheptenyl group, andthe like) which may be optionally substituted respectively by 1 or moregroups selected from hydroxy group, a halogen atom, nitrile group, aC₁₋₆ alkyl group (for example, methyl group, ethyl group, n-propylgroup, iso-propyl group, n-butyl group, iso-butyl group, tert-butylgroup, n-pentyl group, iso-pentyl group, neopentyl group, n-hexyl groupetc.), a C₁₋₆ alkoxy group (for example, methoxy group, ethoxy group,n-propoxy group, iso-propoxy group, sec-propoxy group, n-butoxy group,iso-butoxy group, sec-butoxy group, tert-butoxy group, n-pentoxy group,iso-pentoxy group, sec-pentoxy group, tert-pentoxy group, n-hexoxy groupetc.), a C₁₋₆ alkoxy C₁₋₆ alkyl group, an aralkyl group (for example,benzyl group, phenethyl group, naphthylmethyl group, naphthylethyl groupetc.), and the like.

Preferable examples of the “5 to 14 membered non-aromatic heterocyclicgroup”, “C₆₋₁₄ aromatic hydrocarbocyclic group” and “5 to 14 memberedaromatic heterocyclic group” in “an optionally substituted 5 to 14membered non-aromatic heterocyclic group”, “an optionally substitutedC₆₋₁₄ aromatic hydrocarbocyclic group” and “an optionally substituted 5to 14 membered aromatic heterocyclic group” are not specificallylimited, but the more preferable “5 to 14 membered non-aromaticheterocyclic group” includes pyrrolidinyl group, pyrrolinyl group,piperidinyl group, piperazinyl group, imidazolinyl group, pyrazolylgroup, imidazolidinyl group, morpholinyl group, phthalimidoyl group, asuccinimidoyl group etc.; the more preferable “C₆₋₁₄ aromatichydrocarbocyclic group” includes phenyl group, indenyl group, naphthylgroup, azulenyl group, heptalenyl group, biphenyl group etc.; the morepreferable “5 to 14 membered aromatic heterocyclic group” includespyrrolyl group, pyridyl group, pyridazinyl group, pyrimidinyl group,pyrazinyl group, pyrazolyl group, imidazolyl group, thienyl group, furylgroup, thiazolyl group, iso-thiazolyl group, quinolyl group,iso-quinolyl group, indolyl group, benzimidazolyl group, benzothiazolylgroup, benzoxazolyl group, carbazolyl group, dioxinyl group etc.,respectively. Further, preferable examples of the “substituents” in the“which may optionally have substituents” include 1 or more groupsselected from hydroxy group, a halogen atom (for example, fluorine atom,chlorine atom, bromine atom, iodine atom etc.), nitrile group, a C₁₋₆alkyl group (for example, methyl group, ethyl group, n-propyl group,iso-propyl group, n-butyl group, iso-butyl group, tert-butyl group,n-pentyl group, iso-pentyl group, neopentyl group, n-hexyl group etc.),a C₁₋₆ alkoxy group (methoxy group, ethoxy group, n-propoxy group,iso-propoxy group, sec-propoxy group, n-butoxy group, iso-butoxy group,sec-butoxy group, tert-butoxy group, n-pentoxy group, iso-pentoxy group,sec-pentoxy group, tert-pentoxy group, n-hexoxy group etc.), a C₁₋₆alkoxy C₁₋₆ alkyl group (for example, methoxymethyl group, methoxyethylgroup, ethoxymethyl group, ethoxyethyl group etc.), an aralkyl group(for example, benzyl group, phenethyl group, naphthylmethyl group,naphthylethyl group etc.), and the like. Further, an amino group, acyclic amino group, and an alkoxyamino group which may optionally havesubstituents are also preferable as the substituents.

Q indicates NH, O or S in the formula (I), and is preferably O.

The groups indicated by X, X¹, X² and X³ in the present inventionindicate the same or different single bonding, an optionally substitutedC₁₋₆ alkylene group, an optionally substituted C₂₋₆ alkenylene group, anoptionally substituted C₂₋₆ alkynylene group, —O—, —S—, —CO—, —SO—,—SO₂—, —N(R⁶)—, —N(R⁷)—CO—, —CO—N(R⁸)—, —N(R⁹)—CH₂—, —CH₂—N(R¹⁰)—,—CH₂—CO—, —CO—CH₂—, —N(R¹¹)—S(O)_(m)—, —S(O)_(n)—N(R¹²)—,—CH₂—S(O)_(p)—, —S(O)_(q)—CH₂—, —CH₂—O—, —O—CH₂—, —N(R¹³)—CO—N(R¹⁴)— or—N(R¹⁵)—CS—N(R¹⁶)— (wherein R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵and R¹⁶ indicate hydrogen atom, a C₁₋₆ alkyl group or a C₁₋₆ alkoxygroup; and m, n, p and q indicates an integer of 0, 1 or 2independently).

Specifically preferable examples in the above “C₁₋₆ alkylene group” isan alkenylene group having 1 to 3 carbons, and examples include —CH₂—,—(CH₂)₂—, —CH(CH₃)—, —(CH₂)₃—, —CH(CH₃)—CH₂—, —CH₂—CH(CH₃)— etc.Specifically preferable examples in the above “C₂₋₆ alkenylene group” isan alkenylene group having 2 or 3 carbons, and examples include —CH═CH—,—CH═CH—CH₂—, —CH₂—CH═CH—, —C(CH₃)═CH—, —CH═C(CH₃)— etc. Specificallypreferable examples in the above “C₂₋₆ alkynylene group” is analkynylene group having 2 or 3 carbons, and examples include —C≡C—,—C≡C—CH₂—, —CH₂—C≡C— etc. Preferable examples in the substituentsindicated by X, X¹, X² and X³ in the “C₁₋₆ alkylene group which mayoptionally have substituents”, “C₂₋₆ alkenylene group which mayoptionally have substituents” or “C₂₋₆ alkynylene group which mayoptionally have substituents” include a halogen atom (for example,fluorine atom, chlorine atom, bromine atom, iodine atom etc.), hydroxygroup, nitrile group, nitro group etc.

The preferable C₁₋₆ alkyl group represented by the R⁶, R⁷, R⁸, R⁹, R¹⁰,R¹¹, R¹², R¹³, R¹⁴, R¹⁵ and R¹⁶ includes methyl group, ethyl group,n-propyl group, iso-propyl group, n-butyl group, tert-butyl group etc.,and the preferable C₂₋₆ alkyoxy group includes methoxy group, ethoxygroup, n-propoxy group, iso-propoxy group, n-butoxy group, tert-butoxygroup etc.

The preferable group in X, X¹, X² and X³ in the above formula (I)includes single bond, —CH₂—, —CH(OH)—, —CH(CN)—, —CH₂—CH₂—,—CH(OH)—CH₂—, —CH(CN)—CH₂—, —CH₂—CH(OH)—, —CH₂—CH(CN)—, —CH═CH—,—CH═CH—CH₂—, —CH═CH—CH(OH)—, —CH═CH—CH(CN)—, —CH(OH)—CH═CH—,—CH(CN)—CH═CH—, —C≡C—, —O—, —S—, —SO—, —SO₂—, —CO—, —NH—CO—NH—,—NH—CS—NH—, and the like; the more preferable group includes singlebond, —CH₂—, —CH(OH)—, —CH(CN)—, —CH₂—CH₂—, —CH(OH)—CH₂—, —CH(CN)—CH₂—,—CH₂—CH(OH)—, —CH₂—CH(CN)—, —CH═CH—, —C≡C—, —CO—, and the like; thefurther preferable group are —CH₂—, —CH(OH)—, —CO—, and a single bond ismost preferable.

The preferable mode of in the compound according to the presentinvention represented by the formula:

(wherein Q, R¹, R², R³, R⁴ and R⁵ have the same meanings as definedabove), a salt thereof or hydrates thereof is not specifically limited.Among them, the preferable mode includes the compound, a salt thereof orhydrates thereof, wherein R¹ (namely, 1-position of a pyridone ring) isa group represented by the formula —X-A (X and A have the same meaningsas defined above), two of the residual R², R³, R⁴ and R⁵ are a grouprepresented by the formula —X-A (X and A have the same meanings asdefined above), and the other two are hydrogen atom, a halogen atom or aC₁₋₆ alkyl group; namely, the compound represented by the formula:

(wherein Q, X¹, X², X³, A¹, A², A³, R¹⁷ and R¹⁸ have the same meaningsas defined above), a salt thereof or hydrates thereof. The morepreferable mode includes the compound, a salt thereof or hydratesthereof, wherein Q is oxygen in the above formula (II); namely, thepyridone compound represented by the formula:

(wherein X¹, X², X³, A¹, A², A³, R¹⁷ and R¹⁸ have the same meanings asdefined above), a salt thereof or hydrates thereof. The furtherpreferable mode includes the compound, a salt thereof or hydratesthereof, wherein R¹⁷ and R¹⁸ are hydrogen atoms in the above formula(III); namely, 1,3,5-substituted pyridone compound represented by theformula:

(wherein X¹, X², X³, A¹, A² and A³ have the same meanings as definedabove), a salt thereof or hydrates thereof. The most preferable modeincludes the compound, a salt thereof or hydrates thereof, wherein X¹,X² and X³ are single bonds in the above formula (IV); namely,1,3,5-substituted pyridone compound represented by the formula:

(wherein A¹, A² and A³ have the same meanings as defined above), a saltthereof or hydrates thereof. The preferable groups in A¹, A² and A³ areas in the above exemplification.

There is no particular limitation for “a salt” in the specification ofthe present application so far as it forms a salt with the compound ofthe present invention and is a pharmacologically acceptable one.Preferably, salt with a hydrogen halide (such as hydrofluoride,hydrochloride, hydrobromide or hydroiodide), salt with an inorganic acid(such as sulfate, nitrate, perchlorate, phosphate, carbonate orbicarbonate), salt with an organic carboxylic acid (such as acetate,trifluoroacetate, oxalate, maleate, tartrate, fumarate or citrate), saltwith an organic sulfonic acid (such as methanesulfonate,trifluoromethanesulfonate, ethanesulfonate, benzenesulfonate,toluenesulfonate or camphor-sulfonate), salt with an amino acid (such asaspartate or glutamate), salt with a quaternary amine, salt with analkaline metal (such as sodium salt or potassium salt) and salt with analkaline earth metal (such as magnesium salt or calcium salt). Morepreferred examples of the “pharmacologically acceptable salt” arehydrochloride, oxalate etc.

Representative manufacturing methods for the compounds represented bythe above formula (I) according to the present invention will beillustrated as hereunder.

Production Process 1

Wherein A¹, A² and A³ may be the same as or different from each otherand each indicates optionally substituted C₃₋₈ cycloalkyl group, theC₃₋₈ cycloalkenyl group, 5- to 14-membered non-aromatic heterocyclicgroup, C₆₋₁₄ aromatic hydrocarbocyclic group or 5- to 14-memberedaromatic heterocyclic group; Z¹ and Z² are the same as or different fromeach other and each represents halogen atoms; and X¹, X² and X³ have thesame meanings as defined above. In the present production process, themost preferable A¹, A² and A³ are optionally substituted C₆₋₁₄ aromatichydrocarbocyclic group or 5- to 14-membered aromatic heterocyclic group.The above-mentioned production process 1 is a process of producing thecompound (I-1) which is related to the present invention, by introducingA¹, A² and A³ in the pyridone compound which has the substituents Z¹ andZ². Namely, the compound (I-1) which is related to the present inventioncan be produced by the process that the pyridone compound (i) which hasthe substituents Z¹ and Z² and an aryl boronic acid derivative areprovided to a coupling reaction using a copper compound to obtain thecompound (ii), and then A² and A³ are introduced in the compound (ii) bycarrying out the coupling reaction with an organometallic reagent usinga transition metal catalyst or an organoboron compound, preferablycarrying out the coupling reaction with an aryl tin derivative, an arylzinc derivative or an aryl boronic acid derivative, using a palladiumcatalyst. The preferable aryl boronic acid derivative which is used forthe reaction of producing the compound (ii) differs depending on astarting raw material, a solvent used and the like, and is notspecifically limited unless the reaction is not disturbed, but the arylboronic acid derivative which has a group corresponding to A¹ introducedas an aryl group, such as preferably a phenyl boronic acid derivativewhich may be optionally substituted, a heterocyclic boronic acidderivative which may be optionally substituted, or the like, can beused. Preferable result can be also obtained by the present reaction inthe presence of a base, and at this time, the base used differsdepending on a starting raw material, a solvent used and the like. Whenthe base is used in the coupling reaction of the present reaction, it isnot specifically limited, and preferably triethylamine, pyridine,tetramethylethylenediamine and the like. Preferable examples of thecopper compound used include copper acetate,di-μ-hydroxo-bis[(N,N,N′,N′-tetramethylethylenediamine)copper(II)]chloride, and the like. The more preferable result can be obtainedby carrying out the reaction of producing the compound (ii) from (i) inthe presence of a solvent. The solvent used differs usually depending ona starting raw material, a reagent and the like, and is not specificallylimited so long as it is inert to the reaction and dissolves the rawmaterial in a certain amount. Preferably, dichloromethane,tetrahydrofuran, ethyl acetate and the like may be proposed. Further,the present reaction is preferably carried out under atmosphere ofoxygen or in air flow, and good results (the reduction of the reactiontime and the improvement of yield etc.) can be obtained thereby. Thearyl tin compound, the aryl zinc compound or the aryl boronic acidderivative which is used for the reaction of producing the compound(I-1) by introducing A² and A³ in the compound (ii) differs depending ona starting raw material, a solvent used and the like, and is notspecifically limited unless the reaction is not disturbed, but a phenyltin compound which may be optionally substituted, a heterocyclic tincompound which may be optionally substituted, a phenyl zinc compoundwhich may be optionally substituted, a heterocyclic zinc compound whichmay be optionally substituted, a phenyl boronic acid derivative, aheterocyclic boronic acid derivative which may be optionallysubstituted, an aryl tin compound, an aryl zinc compound or an arylboronic acid derivative which has a group corresponding to A¹ or A²introduced as an aryl group, can be preferably used. Preferable resultcan be also obtained by the present reaction in the presence of a base,and at this time, the base used differs depending on a starting rawmaterial, a solvent used and the like. Further, it is not specificallylimited, unless the reaction is not disturbed, and preferably cesiumcarbonate, sodium carbonate, potassium carbonate, and the like. Thepalladium catalyst used is not specifically limited in usual, and knownpalladium catalysts such as tetrakistriphenylphosphine palladium and thelike are preferably mentioned. The reaction of producing the compound(I-1) by introducing A² and A³ in the compound (ii) is preferablycarried out in the presence of a solvent from the viewpoints ofoperation property and stirring property, and the solvent used is notspecifically limited in usual, but dimethylformamide, toluene, xylene,benzene and the like are preferably mentioned. The reaction temperatureis not specifically limited, and usually room temperature, or underrefluxing by heating, and preferably 50 to 160° C. In addition to them,the compound (I-1) related to the present invention can be also producedby the process that the pyridone compound (iii) after introduction of A¹and A^(2a) is introduced to an organoboron compound or an organometallicreagent, preferably a boronic acid derivative, a tin compound or a zinccompound, and the derivative is provided to a coupling reaction with ahalogenated aryl derivative using a transition metal catalyst,preferably a palladium catalyst.

Production Process 2

Wherein X¹, X², X³, A¹, A², A³, Z¹ and Z² indicate the same meanings asdefined above; and Z³ indicates a protecting group of hydroxy group ofan alcohol (for example, a C₁₋₆ alkyl group, a benzyl group and thelike). In the present production process, the most preferable A¹, A² andA³ are optionally substituted C₆₋₁₄ aromatic hydrocarbocyclic group or5- to 14-membered aromatic heterocyclic group. The compound (I-1)according to the present invention can be also produced by introducingA¹, A² and A³ to the pyridine compound (iv) having substituents Z¹ and—OZ³. The reaction of producing the compound (v) by introducing A³ tothe compound (iv) can be carried out by providing to the couplingreaction with an organometallic reagent or an organoboron compound usinga transition metal catalyst, preferably by providing the compound (iv)to the coupling reaction with an aryl tin derivative, an aryl zincderivative, or an aryl boronic acid derivative in the presence of abase, using a palladium catalyst. The aryl tin derivative, the aryl zincderivative or the aryl boronic acid derivative used for the presentreaction differs depending on a starting raw material, a solvent usedand the like, and is not specifically limited unless the reaction is notdisturbed, but a phenyl tin derivative which may be optionallysubstituted, a heterocyclic tin derivative which may be optionallysubstituted, a phenyl zinc derivative which may be optionallysubstituted, a heterocyclic zinc derivative which may be optionallysubstituted, a phenyl boronic acid derivative, a heterocyclic boronicacid derivative which may be optionally substituted, an aryl tinderivative, an aryl zinc derivative or an aryl boronic acid derivativewhich has a group corresponding to A³ introduced as an aryl group, canbe preferably used. The base used differs depending on a starting rawmaterial, a solvent used and the like and is not specifically limitedunless the reaction is not disturbed, but preferably cesium carbonate,sodium carbonate, potassium carbonate, and the like. The palladiumcatalyst used is not specifically limited in usual, and known palladiumcomplex such as tetrakistriphenylphosphine palladium and the like arepreferably mentioned. Further, the present reaction is preferablycarried out in the presence of a solvent from the viewpoints ofoperation property and stirring property. The solvent used differsdepending on a starting material, a solvent used and the like, and thosewhich dissolve the starting material to a certain degree are notspecifically limited unless the reaction is not disturbed, butdimethylformamide, toluene, xylene, benzene and the like are preferablymentioned. The reaction temperature is not specifically limited, andusually room temperature, or under refluxing by heating, and preferably50 to 160° C. The reaction of producing the pyridone compound (vi) byde-protecting of Z³ can be carried out by some known processes, and forexample, a conventional process described in T. W. Greene and P. G. M.Wuts “Protecting groups in organic synthesis 2^(nd) Edition (1991)” ismentioned as the representative process. The reaction of producing thepyridone compound (vii) by introducing the substituent Z² to thecompound (vi) can be usually carried out by a known halogenation method.The halogenating agent differs depending on a starting raw material, asolvent used and the like and is not specifically limited unless thereaction is not disturbed, but a bromination agent such as aceticacid-bromine, N-bromosuccinimide or the like, an iodination agent suchas iodine, N-iodosuccinimide or the like, and the like are preferablyused. The compound (viii) can be produced by providing the compound(vii) and an aryl boronic acid derivative to the coupling reaction usinga copper compound and by introducing A¹. The aryl boronic acidderivative used is not specifically limited in usual, and an arylboronic acid derivative which may be optionally substituted, aheterocyclic boronic acid derivative which may be optionallysubstituted, and an aryl boronic acid derivative which has a groupcorresponding to A¹ introduced as an aryl group, can be used. Preferableresult can be also obtained by the present reaction in the presence of abase, and at this time, the base used differs depending on a startingraw material, a solvent used and the like. Further, the base is notspecifically limited, and preferably triethylamine, pyridine,tetramethylethylenediamine and the like. Preferable examples of thecopper compound used include copper acetate,di-μ-hydroxo-bis[(N,N,N′,N′-tetramethylethylenediamine)copper(II)]chloride, and the like. Further, the present reaction is preferablycarried out in the presence of a solvent. The solvent used differsusually depending on a starting raw material, a reagent and the like,and is not specifically limited so long as it is inert to the reactionand dissolves the starting materials in a certain amount, but ispreferably dichloromethane, tetrahydrofuran, ethyl acetate and the like.Further, the present reaction is preferably carried out under atmosphereof oxygen or in air flow, and good results (the reduction of thereaction time and the improvement of yield etc.) can be obtainedthereby. The final step of producing the compound (I-1) related to thepresent invention can be carried out by providing the compound (viii) tothe coupling reaction with an organometallic reagent or an organoboroncompound using a transition metal catalyst, preferably by providing tothe coupling reaction with an aryl tin derivative, an aryl zincderivative or an aryl boronic acid derivative using a palladiumcatalyst, and by introducing A² to the compound (viii). The aryl tinderivative, the aryl zinc derivative or the aryl boronic acid derivativewhich is used is not specifically limited usually, and a phenyl tinderivative which may be optionally substituted, a heterocyclic tinderivative which may be optionally substituted, a phenyl zinc derivativewhich may be optionally substituted, a heterocyclic zinc derivativewhich may be optionally substituted, a phenyl boronic acid derivative, aheterocyclic boronic acid derivative which may be optionallysubstituted, an aryl tin derivative, an aryl zinc derivative or an arylboronic acid derivative which has a group corresponding to A² introducedas an aryl group, can be preferably used. The sequential reaction ofproducing (I-1) from (viii) which was mentioned in the productionprocess 2 can also obtain a preferable result in the presence of a base,and at this time, the base used differs depending on a starting rawmaterial, a solvent used and the like. Further, it is not specificallylimited, unless the reaction is not disturbed, and preferably cesiumcarbonate, sodium carbonate, potassium carbonate, and the like. Thepalladium catalyst used is not specifically limited in usual, and knownpalladium catalysts such as tetrakistriphenylphosphine palladium and thelike are preferably mentioned. Further, a more preferable result can beobtained by carrying out the present reaction in the presence of asolvent, and the solvent used is not specifically limited in usual, andthe solvent used differs depending on a starting raw material, a reagentand the like, and the solvent which does not disturb the reaction anddissolves the starting raw material to a certain degree is notspecifically limited, but is preferably dimethylformamide, toluene,xylene, benzene and the like. The reaction temperature is notspecifically limited, and usually room temperature, or under refluxingby heating, and preferably 50 to 160° C. In addition to them, thecompound (I-1) related to the present invention can be also produced bythe process that the pyridone compound (viii) after introduction ofA^(1a) is introduced to an organoboron compound or an organometallicreagent, preferably a boronic acid derivative, a tin compound or a zinccompound, and the derivative is provided to a coupling reaction with ahalogenated aryl derivative using a transition metal catalyst,preferably a palladium catalyst.

Production Process 3

Wherein X¹, X², X³, A¹, A², A³, Z¹ and Z² have the same meanings asdefined above, and each of the most preferable group of A¹, A² and A³ inthe present production process is the C₆₋₁₄ aromatic hydrocarbocyclicgroup or the 5 to 14 membered aromatic heterocyclic group which mayoptionally have substituents, respectively. The compound (I-1) accordingto the present invention can be also produced by introducing A¹, A² andA³ to 2-hydroxypyridine. The reaction of producing the compound (ix) canbe conducted by providing an aryl boronic acid derivative to thecoupling reaction using a copper compound, the Ullmann reaction with ahalogenated aryl derivative, or a substitution reaction for thehalogenated aryl derivative and by introducing A¹ to 2-hydroxypyridine.The aryl boronic acid derivative used in the coupling reaction differsusually depending on a starting raw material, a reagent and the like,and is not specifically limited unless the reaction is not disturbed.The aryl boronic acid derivative having a group corresponding to A¹introduced as an aryl group such as a phenyl boronic acid derivativewhich may be optionally substituted, a heterocyclic boronic acidderivative which may be optionally substituted, and the like can bepreferably used. Preferable result can be also obtained by the presentreaction in the presence of a base, and at this time, the base useddiffers depending on a starting raw material, a solvent used and thelike. Further, the base is not specifically limited unless the reactionis not disturbed, but is preferably triethylamine, pyridine,tetramethylethylenediamine and the like. Preferable examples of thecopper compound used include copper acetate,di-μ-hydroxo-bis[(N,N,N′,N′-tetramethylethylenediamine) copper(II)]chloride, and the like. Further, the present reaction is preferablycarried out in the presence of a solvent. The solvent used differsusually depending on a starting raw material, a reagent and the like,and the solvent which does not disturb the reaction and dissolves thestarting raw material to a certain degree is not specifically limited,but is preferably dichloromethane, tetrahydrofuran, ethyl acetate andthe like. Further, the present reaction is preferably carried out underatmosphere of oxygen or in air flow, and good results (the reduction ofthe reaction time and the improvement of yield etc.) can be obtainedthereby. The Ullmann reaction is carried out at 60° C. to underrefluxing by heating, preferably 100 to 200° C. in the presence of abase such as potassium carbonate, sodium carbonate or sodium acetate,using copper or a copper compound such as copper iodide, copperchloride, copper bromide or the like, which is not specifically limitedusually. The solvent used differs depending on a starting raw material,a reagent and the like, and the solvent which does not disturb thereaction and dissolves the starting raw material to a certain degree isnot specifically limited, but is preferably dimethylformamide, toluene,xylene, tetralin, dichlorobenzene, nitrobenzene and the like. Thesubstitution reaction with the halogenated aryl derivative is notspecifically limited, but carried out under ice-cooling to underrefluxing by heating, preferably at room temperature to 60° C. in asolvent such as tetrahydrofuran or dimethylformamide or the like, usinga base such as potassium carbonate, sodium hydride, potassium hydride,sodium butoxide, or potassium butoxide or the like. The reaction ofproducing the compound (x) by introducing the substituent Z¹ to thecompound (ix) can be usually carried out by known halogenation method.The halogenating agent used differs depending on a starting rawmaterial, a solvent used and the like, and is not specifically limited,unless the reaction is not disturbed, but a bromination agent such asacetic acid-bromine, N-bromosuccinimide or the like, an iodination agentsuch as iodine, N-iodosuccinimide or the like, and the like arepreferably used. The reaction of producing the compound (xi) byintroducing A³ to the compound (x) can be usually carried out byproviding the compound (x) to the coupling reaction with anorganometallic reagent or an organoboron compound using a transitionmetal catalyst, preferably by providing it to the coupling reaction withan aryl tin derivative, an aryl zinc derivative, or an aryl boronic acidderivative in the presence of a base, using a palladium catalyst. Thearyl tin derivative, the aryl zinc derivative or the aryl boronic acidderivative which is used for the present reaction is not specificallylimited usually, but an aryl tin derivative, an aryl zinc derivative oran aryl boronic acid derivative having a group corresponding to A³introduced as an aryl group such as a phenyl tin derivative which may beoptionally substituted, a heterocyclic tin derivative which may beoptionally substituted, a phenyl zinc derivative which may be optionallysubstituted, a heterocyclic zinc derivative which may be optionallysubstituted, a phenyl boronic acid derivative, a heterocyclic boronicacid derivative which may be optionally substituted, can be preferablyused. The base used differs depending on a starting raw material, asolvent used and the like and is not specifically limited unless thereaction is not disturbed, but preferably cesium carbonate, sodiumcarbonate, potassium carbonate, and the like. The palladium catalystused is not specifically limited in usual, and known palladium catalystssuch as tetrakistriphenylphosphine palladium and the like are preferablymentioned. Further, the present reaction is preferably carried out inthe presence of a solvent from the viewpoints of operation property andstirring property. The solvent used differs depending on a startingmaterial, a solvent used and the like, and the solvent which does notdisturb the reaction and dissolves the starting material to a certaindegree is not specifically limited, but is preferably dimethylformamide,toluene, xylene, benzene and the like. The reaction temperature is notspecifically limited, and usually room temperature, or under refluxingby heating, and preferably 50 to 160° C. The reaction of producing thecompound (xii) by introducing the substituent Z² to the compound (xi)can be usually carried out by known halogenation method. Thehalogenating agent used differs depending on a starting raw material, asolvent used and the like, and is not specifically limited, unless thereaction is not disturbed, but a bromination agent such as aceticacid-bromine, N-bromosuccinimide or the like, an iodination agent suchas iodine, N-iodosuccinimide or the like, and the like are preferablyused. The final step of producing the compound (I-1) related to thepresent invention can be carried out by providing the compound (xii) tothe coupling reaction with an organometallic reagent or an organoboroncompound using a transition metal catalyst, preferably by providing itto the coupling reaction with an aryl tin derivative, an aryl zincderivative or an aryl boronic acid derivative using a palladiumcatalyst, and by introducing A² to the compound (xii). The aryl tinderivative, the aryl zinc derivative or the aryl boronic acid derivativewhich is used differs depending on a starting raw material, a solventused and the like, and is not specifically limited unless the reactionis not disturbed. The aryl tin derivative, aryl zinc derivative or arylboronic acid derivative having a group corresponding to A^(2a)introduced as an aryl group, such as a phenyl tin derivative which maybe optionally substituted, a heterocyclic tin derivative which may beoptionally substituted, a phenyl zinc derivative which may be optionallysubstituted, a heterocyclic zinc derivative which may be optionallysubstituted, a phenyl boronic acid derivative, a heterocyclic boronicacid derivative which may be optionally substituted, can be used. Atthis time, the base used differs depending on a starting raw material, asolvent used and the like, and is not specifically limited unless thereaction is not disturbed, but is preferably cesium carbonate, sodiumcarbonate, potassium carbonate, and the like. The palladium catalystused differs depending on a starting raw material, a solvent used andthe like, and is not specifically limited unless the reaction is notdisturbed, but known palladium catalysts such astetrakistriphenylphosphine palladium and the like are mentioned.Further, a more preferable result can be obtained by carrying out thepresent reaction in the presence of a solvent, and the solvent used isnot specifically limited in usual, but is preferably dimethylformamide,toluene, xylene, benzene and the like. The reaction temperature is notspecifically limited, and usually room temperature, or under refluxingby heating, and preferably 50 to 160° C. In addition to them, thecompound (I-1) related to the present invention can be also produced bythe process that the compound (xii) is introduced to an organoboroncompound or an organometallic reagent, preferably a boronic acidderivative, a tin compound or a zinc compound or the like, and thederivative is provided to a coupling reaction with a halogenated arylderivative using a transition metal catalyst, preferably a palladiumcatalyst.

Production Process 4

Wherein X¹, X², X³, A¹, A², A³, Z¹, Z² and Z³ have the same meanings asdefined above, and each of the most preferable group of A¹, A² and A³ inthe present production process is the C₆₋₁₄ aromatic hydrocarbocyclicgroup or the 5 to 14 membered aromatic heterocyclic group which mayoptionally have substituents, respectively. The compound (I-1) relatedto the present invention can be also produced by introducing A¹, A² andA³ to the compound (xiii) having the substituents Z¹, Z² and —OZ³. Thereaction of producing the compound (xiv) by introducing A² to thecompound (xiii) can be conducted by providing the compound (xiii) to thecoupling reaction with an organometallic reagent or an organoboroncompound using a transition metal catalyst, preferably by providing itto the coupling reaction with an aryl tin derivative, an aryl zincderivative, or an aryl boronic acid derivative in the presence of abase, using a palladium catalyst. The aryl tin compound, aryl zinccompound or aryl boronic acid derivative used in the present reactiondiffers usually depending on a starting raw material, a reagent and thelike, and is not specifically limited unless the reaction is notdisturbed. The ary tin compound, aryl zinc compound or aryl boronic acidderivative having a group corresponding to A² introduced as an arylgroup, such as a phenyl tin derivative which may be optionallysubstituted, a heterocyclic tin derivative which may be optionallysubstituted, a phenyl zinc derivative which may be optionallysubstituted, a heterocyclic zinc derivative which may be optionallysubstituted, a phenyl boronic acid derivative, a heterocyclic boronicacid derivative which may be optionally substituted and the like can beused. The base used differs depending on a starting raw material, asolvent used and the like and is not specifically limited unless thereaction is not disturbed, but is cesium carbonate, sodium carbonate,potassium carbonate, and the like. The palladium catalyst used differsdepending on a starting raw material, a solvent used and the like and isnot specifically limited unless the reaction is not disturbed, but knownpalladium catalysts such as tetrakistriphenylphosphine palladium and thelike are mentioned. Further, the present reaction is preferably carriedout in the presence of a solvent from the viewpoints of operationproperty and stirring property. The solvent used differs depending on astarting material, a solvent used and the like, and the solvent whichdoes not disturb the reaction and dissolves the starting material to acertain degree is not specifically limited, but is preferablydimethylformamide, toluene, xylene, benzene and the like. The reactiontemperature is not specifically limited, and usually room temperature,or under refluxing by heating, and preferably 50 to 160° C. The reactionof producing the compound (xv) by introducing the substituent A³ to thecompound (xiv) can be carried out by providing the compound (xiv) to thecoupling reaction with an organometallic reagent or an organoboroncompound using a transition metal catalyst, preferably by providing itto the coupling reaction with an aryl tin compound, aryl zinc compound,or aryl boronic acid derivative in the presence of a base, using apalladium catalyst. The aryl tin compound, aryl zinc compound or arylboronic acid derivative used in the present reaction differs usuallydepending on a starting raw material, a reagent and the like, and is notspecifically limited unless the reaction is not disturbed. The aryl tincompound, aryl zinc compound or aryl boronic acid derivative having agroup corresponding to A³ introduced as an aryl group, such as a phenyltin derivative which may be optionally substituted, a heterocyclic tinderivative which may be optionally substituted, a phenyl zinc derivativewhich may be optionally substituted, a heterocyclic zinc derivativewhich may be optionally substituted, a phenyl boronic acid derivative, aheterocyclic boronic acid derivative which may be optionally substitutedand the like can be preferably used. The base used differs depending ona starting raw material, a solvent used and the like and is notspecifically limited unless the reaction is not disturbed, but ispreferably cesium carbonate, sodium carbonate, potassium carbonate, andthe like. The palladium catalyst used is not specifically limitedusually, but known palladium catalysts such astetrakistriphenylphosphine palladium and the like are preferablymentioned. Further, the present reaction is preferably carried out inthe presence of a solvent from the viewpoints of operation property andstirring property. The solvent used differs depending on a startingmaterial, a solvent used and the like, and the solvent which does notdisturb the reaction and dissolves the starting material to a certaindegree is not specifically limited, but is preferably dimethylformamide,toluene, xylene, benzene and the like. The reaction temperature is notspecifically limited, and usually room temperature, or under refluxingby heating, and preferably 50 to 160° C. The reaction of producing thepyridone compound (xvi) by de-protecting the removal of Z³ can becarried out by some known processes, and for example, a conventionalprocess described in T. W. Greene and P. G. M. Wuts “Protecting groupsin organic synthesis 2^(nd) Edition (1991)” is mentioned as therepresentative process. The final step of producing the compound (I-1)related to the present invention can be conducted by providing thecompound (xvi) and an aryl boronic acid derivative to the couplingreaction using a copper compound, the Ullmann reaction with ahalogenated aryl derivative, or a substitution reaction for thehalogenated aryl derivative and by introducing A¹. The aryl boronic acidderivative used differs depending on a starting raw material, a solventused and the like, and is not specifically limited unless the reactionis not disturbed. The aryl boronic acid derivative having a groupcorresponding to A¹ introduced as an aryl group, such as a phenylboronic acid derivative which may be optionally substituted, aheterocyclic boronic acid derivative which may be optionally substitutedand the like can be used. Preferable result can be also obtained by thepresent reaction in the presence of a base, and at this time, the baseused differs depending on a starting raw material, a solvent used andthe like. Further, the base is not specifically limited unless thereaction is not disturbed, but is preferably triethylamine, pyridine,tetramethylethylenediamine and the like. Preferable examples of thecopper compound used include copper acetate,di-μ-hydroxo-bis[(N,N,N′,N′-tetramethylethylenediamine) copper(II)]chloride, and the like. Further, the present reaction is preferablycarried out in the presence of a solvent. The solvent used differsusually depending on a starting raw material, a reagent and the like,and the solvent which does not disturb the reaction and dissolves thestarting raw material to a certain degree is not specifically limited,but is preferably dichloromethane, tetrahydrofuran, ethyl acetate andthe like. Further, the present reaction is preferably carried out underatmosphere of oxygen or in air flow, and good results (the reduction ofthe reaction time and the improvement of yield etc.) can be obtainedthereby. The Ullmann reaction is carried out at 60° C. to underrefluxing by heating, preferably 100 to 200° C. in the presence of abase such as potassium carbonate, sodium carbonate or sodium acetate,using copper or a copper compound such as copper iodide, copperchloride, copper bromide or the like, which is not specifically limitedusually. The solvent used differs depending on a starting raw material,a reagent and the like, and the solvent which does not disturb thereaction and dissolves the starting raw material to a certain degree isnot specifically limited, but is preferably dimethylformamide, toluene,xylene, tetralin, dichlorobenzene, nitrobenzene and the like. Thesubstitution reaction with the halogenated aryl derivative is notspecifically limited, but carried out under ice-cooling to underrefluxing by heating, preferably at room temperature to 60° C. in asolvent such as tetrahydrofuran or dimethylformamide or the like, usinga base such as potassium carbonate, sodium hydride, potassium hydride,sodium butoxide, or potassium butoxide or the like.

In the above production process, the production intermediate representedby the formula:

(wherein A^(1a), A^(3a) and W have the same meanings as defined above)can be also produced by the following method (Production process 5).Production Process 5

W, W′ and W″ in the above formula indicate the same or different halogenatom, and the most preferable atom is bromine atom.

The compound (XII) can be easily produced according to known methods orcorresponding methods, and further, can be easily obtained as acommercially available substance. The step of producing the compound(XI) from the compound (XII) is a step of reacting the compound (XII)with the base represented by the formula Z³OM (M indicates an alkalimetal atom). The base differs depending on a starting raw material, asolvent used and the like, and is not specifically limited unless thereaction is not disturbed, but is preferably sodium alkoxide, andpreferably sodium methoxide, sodium ethoxide and the like in particular.In this case, it is preferable to carry out the reaction in an alcoholcorresponding to the alkoxide used, and for example, it is preferable tocarry out in methanol in case of using sodium methoxide and ethanol incase of using sodium ethoxide, etc.

The step of producing the compound (X) from the compound (XI) is a stepof reacting the compound (XI) with trimethoxyborane in the presence of abase. The base used differs depending on a starting raw material, asolvent used and the like, and is not specifically limited unless thereaction is not disturbed, but is preferably n-butyllithium and thelike. The solvent used differs depending on a starting raw material, asolvent used and the like, and the solvent which does not disturb thereaction and dissolves the starting material to a certain degree is notspecifically limited, but is preferably ethers such as tetrahydrofuran,and the like. When n-butyllithium is used as a base, the reaction can beterminated by an acid such as hydrochloric acid, or the like accordingto a conventional method.

The step of producing the compound (IX) from the compound (X) is a stepof carrying out the coupling reaction of the compound (X) with ahalogenoaryl or a halogenoheteroaryl which corresponds to thesubstituent A^(3a) introduced, in the presence of a base and a palladiumcatalyst and producing the compound (IX). The palladium catalyst used isnot specifically limited, but palladium acetate/triphenylphosphinecatalyst and the like can be mentioned as the preferable example. Thebase used differs depending on a starting raw material, a solvent usedand the like, and is not specifically limited unless the reaction is notdisturbed, but is preferably cesium carbonate, sodium carbonate,potassium carbonate, and the like. Further, the present step ispreferably carried out in the presence of a solvent from the viewpointsof operation property and stirring property. The solvent used differsdepending on a starting raw material, a solvent used and the like, andthe solvent which does not disturb the reaction and dissolves thestarting material to a certain degree is not specifically limited, butis preferably 1,2-dimethoxyethane, dimethylformamide, toluene, xylene,benzene and the like. The reaction temperature is not specificallylimited, and usually room temperature, or under refluxing by heating,and preferably 50 to 160° C.

The step of producing the compound (VIII) from the compound (IX) is astep of submitting to the reaction of protecting the removal of Z³ ofthe compound (IX). The present step can be carried out by some knownprocesses, and for example, a method of refluxing the compound (IX) byheating in the presence of an acid (preferably, hydrochloric acid andthe like) is mentioned. Additionally, for example, a conventionalprocess described in T. W. Greene and P. G. M. Wuts “Protecting groupsin organic synthesis 2^(nd) Edition (1991)” is mentioned as therepresentative process.

The step of producing the compound (VI) from the compound (VIII) is astep of submitting the compound (VIII) and the aryl boronic acidderivative represented by the formula A^(1a)B(OH)₂ to the couplingreaction using a copper compound and introducing A^(1a). The arylboronic acid derivative used is not specifically limited usually. Thearyl boronic acid derivative which has a group corresponding to A^(1a)introduced as an aryl group, such as a phenyl boronic acid derivativewhich may be optionally substituted, a heterocyclic boronic acidderivative which may be optionally substituted and the like can be used.Preferable result can be also obtained by the present reaction in thepresence of a base, and at this time, the base used differs depending ona starting raw material, a solvent used and the like. Further, the baseis not specifically limited unless the reaction is not disturbed, but ispreferably triethylamine, pyridine, tetramethylethylenediamine and thelike. Preferable examples of the copper compound used include copperacetate, di-μ-hydroxobis[(N,N,N′,N′-tetramethylethylenediamine)copper(II)]chloride, and the like. Further, the present reaction is preferablycarried out in the presence of a solvent. The solvent used differsusually depending on a starting raw material, a reagent and the like,and the solvent which does not disturb the reaction and dissolves thestarting raw material to a certain degree is not specifically limited,but is preferably N,N-dimethylformamide, dichloromethane,tetrahydrofuran, ethyl acetate and the like. Further, the presentreaction is preferably carried out under atmosphere of oxygen or in airflow, and good results (the reduction of the reaction time and theimprovement of yield etc.) can be obtained thereby.

The step of producing the compound (VII) from the compound (VI) is astep of submitting the compound (VI) to the halogenation reaction. Thehalogenation reaction can be usually carried out by known halogenationmethods. The halogenating agent used differs depending on a starting rawmaterial, a solvent used and the like, and is not specifically limitedunless the reaction is not disturbed, but is preferably a brominationagent such as acetic acid-bromine, N-bromosuccinimide or the like, aniodination agent such as iodine, N-iodosuccinimide or the like, and thelike.

According to the above production process 5, the productionintermediates (VI) and (VII) can be produced in high yield. Further,when the production intermediates the production intermediates of thecompounds related to the present invention are produced according to theproduction processes, the contamination of a copper compound to thefinal product can be easily prevented, and the compounds of the presentinvention satisfying the point of safety (toxicity and the like) can beprovided. Accordingly, the production processes are extremely excellentproduction processes from the viewpoints of yield and safety,experimentally and industrially. The novel compound represented by theformula:

(wherein A^(1a) and A^(3a) are the same as or different from each otherand each indicates a C₆₋₁₄ aromatic hydrocarbocyclic group or 5 to 14membered aromatic heterocyclic group which may optionally have asubstituent, respectively; and R indicates hydrogen atom or a halogenatom) or a salt thereof is useful as the production intermediate in theproduction of the compound (I) according to the present invention or asalt thereof. In the formula (XIII), the preferable examples in A^(1a)and A^(3a) may be the same as or different from each other, and eachincludes phenyl group, pyridyl group, pyridazinyl group, pyrimidinylgroup, pyrazyl group, thienyl group, thiazolyl group, furyl group,naphthyl group, quinolyl group, iso-quinolyl group, indolyl group,benzimidazolyl group, benzothiazolyl group, benzoxazolyl group,imidazopyridyl group, carbazolyl group etc., which may optionally havesubstituents, respectively. The more preferable examples may be the sameas or different from each other, and each includes a phenyl group,pyridyl group, pyrimidinyl group, thienyl group, furyl group etc., whichmay optionally have substituents, respectively. Further, the preferableexamples in R in particular are hydrogen atom or bromine atom.

The substituents on A¹, A² and A³ in the compound represented by theformula:

(wherein Q, X¹, X², X³, A¹, A² and A³ have the same meanings as definedabove; Y¹, Y² and Y³ indicates the same or different substituents; andeach of the most preferable group in A¹, A² and A³ is a C₆₋₁₄ aromatichydrocarbocyclic group or 5 to 14 membered aromatic heterocyclic groupwhich may optionally have substituents, respectively) can be convertedby various reactions. For example, the representative processes are asbelow. That is, various reactions are known for changing to a functionalgroup from a nitro group when (1) Y¹, Y² and/or Y³ are/is nitro group(s)and, although there is no particular limitation for the method and forthe resulting substance, a method of changing to an amine derivative bya reduction reaction may be exemplified. Although there is usually noparticular limitation for the reduction condition, preferred conditionsare a method where iron, zinc or tin is used under acidic conditions, ahydrogenation method where palladium, rhodium, ruthenium, platinum or acomplex thereof is used as a catalyst. When the amine derivativeproduced by the said reduction reaction is used, it is possible tofurther change to an amide compound, a carbamate compound, a sulfonamidecompound, a halogen compound, a substituted amine compound etc., easily.(2) When Y¹, Y² and/or Y³ are/is alkoxy group(s), an example forchanging to a functional group from an alkoxy group is a method tochange to an alcohol derivative by means of deprotection. The alcoholderivative which is prepared by the said method may be easily changed toan ester compound by a dehydrating condensation with carboxylic acidderivative or by a reaction with an acid chloride or may be easilychanged to an ether compound by a Mitsunobu reaction or by acondensation reaction with a halogen compound. (3) When Y¹, Y² and/or Y³are/is aldehyde group(s), various reactions are known for changing to afunctional group from an aldehyde group and, although there is noparticular limitation for the method therefor and the resultingsubstance by the change, an example is a method of changing to acarboxylic acid derivative by an oxidation reaction. The carboxylic acidderivative prepared by the said method may be easily changed further toan ester compound, a ketone compound, etc. In addition, starting fromthe said carboxylic acid derivative, it is possible to easilymanufacture an alcohol derivative by a reduction reaction, an aminederivative by a reductive amination reaction, a secondary alcoholcompound by an addition reaction with an organic metal reagent andvarious alkyl derivatives by a Wittig reaction. (4) When Y¹, Y² and/orY³ are/is halogen atom(s), an example for changing to a functional groupfrom a halogen atom as a substituent is a method of changing to anitrile derivative by a substitution reaction. Besides the above, it isalso possible to easily change to various kinds of compounds via, forexample, an organolithium compound, an organomagnesium compound, anorganotin compound or an organoboronic acid derivative etc.

The above-mentioned methods is the method for the manufacture of thecompound (I) of the present invention. The starting compound in theabove-mentioned methods may form a salt or a hydrate and there is noparticular limitation for such salt and hydrate so far as they do notinhibit the reaction. When the compound (I) of the present invention isobtained in a free substance, it may be changed to a state of a salt byconventional methods. Further, various isomers (for example, ageometrical isomer, an enantiomer based on an asymmetric carbon, arotamer, a stereoisomer, a tautomer, and the like) which are obtainedfor the compound (I) related to the present invention are purified byusing usual separation procedures, for example, such asrecrystallization, a diastereomer salt method, an enzymolysis method,various chromatographies (for example, thin layer chromatography, columnchromatography, gas chromatography, and the like), and can be separated.

The compound of the present invention represented by the above formula(I), a salt thereof or hydrates thereof may be made into pharmaceuticalpreparations such as tablets, diluted powder, fine granules, granules,coated tablets, capsules, syrup, troche, inhalation preparation,suppositories, injections, ointments, eye ointments, eye drops, nasalpreparations, ear drops, cataplasma or lotions by means of conventionalmethods. In the manufacture of the pharmaceutical preparations, it ispossible to use commonly used fillers, binders, disintegrating agent,lubricants, coloring agents, corrigents and, if necessary, stabilizers,emulsifiers, absorption promoters, surfactant, pH adjusting agents,antiseptics, antioxidants, etc. and, after compounding with theingredients commonly used as materials for the pharmaceuticalpreparations, it is made into pharmaceutical preparations by a commonmethod. Examples of the components therefor are 1) animal and plant oilsuch as soybean oil, beef tallow or synthetic glyceride; 2) hydrocarbonsuch as liquid paraffin, squalane or solid paraffin; 3) ester oil suchas octyldodecyl myristate or isopropyl myristate; 4) higher alcohol suchas cetostearyl alcohol or behenyl alcohol; 5) silicone resin; 6)silicone oil; 7) surfactant such as polyoxyethylene fatty acid ester,sorbitan fatty acid ester, glycerol fatty acid ester, polyoxyethylenesorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil orpolyoxyethylene-polyoxypropylene block copolymer; 8) water-solublehigh-molecular substance such as hydroxyethyl cellulose, polyacrylicacid, carboxyvinyl polymer, polyethylene glycol, polyvinylpyrrolidone ormethylcellulose; 9) lower alcohol such as ethanol or isopropanol; 10)polyhydric alcohol such as glycerol, propylene glycol, dipropyleneglycol or sorbitol; 11) saccharide such as glucose or sucrose; 12)inorganic powder such as silicic acid anhydride, aluminum magnesiumsilicate or aluminum silicate; 13) pure water and the like. Applicableexamples of (1) a filler are lactose, corn starch, pure sugar, glucose,mannitol, sorbitol, crystalline cellulose, silicon dioxide etc.; thoseof (2) a binder are polyvinyl alcohol, polyvinyl ether, methylcellulose, ethyl cellulose, gum arabic, tragacanth, gelatin, shellac,hydroxypropyl methyl cellulose, hydroxypropyl cellulose,polyvinylpyrrolidone, polypropylene glycol-polyoxyethylene blockcopolymer, meglumine, calcium citrate, dextrin, pectin etc.; those of(3) a disintegrating agent are starch, agar, gelatin powder, crystallinecellulose, calcium carbonate, sodium bicarbonate, calcium citrate,dextrin, pectin, carboxymethyl cellulose calcium etc.; those of (4) alubricant are magnesium stearate, talc, polyethylene glycol, silica,hydrogenated plant oil etc.; those of (5) a coloring agent are thosewhich are allowed to add to pharmaceuticals; those of (6) a corrigentare cocoa powder, menthol, aromatic powder, peppermint oil, borneol andcinnamon powder; and those of (7) an antioxidant are those which arepermitted to be added to pharmaceuticals, such as ascorbic acid,α-tocopherol and the like, are respectively used.

(1) In the manufacture of preparations for oral use, the compound of thepresent invention or a pharmacologically acceptable salt is mixed with afiller and, if necessary, further with a binder, a disintegrating agent,a lubricant, a coloring agent, a corrigent, etc. and the mixture is madeinto diluted powder, fine particles, granules, tablets, coated tablets,capsules, etc. by a common method. (2) In case of tablets and coatedtablets, there is of course no problem that such tablets and granulesare sugar-coated, gelatin-coated, or appropriately coated uponnecessity. (3) In case of the manufacture of liquid preparations such assyrup, injection preparations and eye drops, a pH adjusting agent, asolubilizer, an isotonizing agent, etc. and, if necessary, asolubilizing aid, a stabilizer, buffer, suspending agent, antioxidantetc. are added, and then made into pharmaceutical preparations by acommon method. It can be made as a freeze drying product, and ainjections can be dosed in vena, subcutis, and muscle. Preferableexamples in a suspending agent include methyl cellulose, polysorbate 80,hydroxyethyl cellulose, gum arabic, tragacanth powder, sodiumcarboxymethyl cellulose, polyoxyethylene sorbitan monolaurate, and thelike; preferable examples in a resolving aid include polyoxyethylenehardened castor oil, polysorbate 80, nicotinic acid amide,polyoxyethylene sorbitan monolaurate, and the like; preferable examplesin a stabilizer include sodium sulfite, meta sodium sulfite, ether, andthe like; preferable examples in a preservative include methylp-oxybenzoate, ethyl p-oxybenzoate, sorbic acid, phenol, cresol,chlorocresol and the like. Further, (4) in case of external use, thereis no particular limitation for a method of manufacturing apharmaceutical preparation, but a common method is used for themanufacture. Thus, with regard to a base material used, variousmaterials which are commonly used for pharmaceuticals, quasi drugs,cosmetics, etc. may be used. Specific examples of the base material usedare animal/plant oil, mineral oil, ester oil, waxes, higher alcohols,fatty acids, silicone oil, surfactant, phospholipids, alcohols,polyhydric alcohols, water-soluble high-molecular substances, clayminerals and pure water and, if necessary, it is possible to add pHadjusting agent, antioxidant, chelating agent, antiseptic antifungal,coloring agent, perfume, etc. If necessary, it is further possible tocompound other components such as a component having adifferentiation-inducing action, blood flow promoter, bactericide,anti-inflammatory agent, cell activator, vitamins, amino acid,moisturizer and keratin solubilizing agent.

Dose of the pharmaceutical agent according to the present inventionvaries depending upon degree of symptom, age, sex, body weight, dosageform, type of salt, sensitivity to the pharmaceuticals, specific type ofthe disease, etc. and, in the case of adults, the daily dose is usuallyabout 30 μg to 10 g, preferably, 100 μg to 5 g or, more preferably, 100μg to 100 mg in the case of oral administration while, in the case ofadministration by injection, it is usually about 30 μg to 1 g,preferably 100 μg to 500 mg or, more preferably, 100 μg to 30 mg. Thatis administered once daily or in several portions a day.

In accordance with the present invention, it is possible to provide anovel compound (I) which show an excellent inhibiting action to AMPAreceptor and/or kainate receptor and are useful as pharmaceuticalagents. Further, a useful production process for producing the compoundor its salt and a production intermediate could be provided. Accordingto this process, the compound relating to the present invention can beobtained in high yield, and the highly safe compound can be obtained.The compound (I) of the present invention suppress the neurotoxicity ofexcitatory neurotransmitters and is able to achieve an excellentneuroprotecting action as a pharmaceutical agent. Accordingly, thecompounds of the present invention are useful as therapeutic, preventiveand improving agents for various nervous diseases and are useful, forexample, as therapeutic and preventive agents for acuteneurodegenerative diseases (such as cerebrovascular disorders at acutestage, subarachnoid hemorrhage, head injury, spinal cord injury,neuropathy caused by hypoxia or hypoglycemia etc.), chronicneurodegenerative diseases (such as Alzheimer's disease, Parkinson'sdisease, Huntington's chorea, amyotrophic lateral sclerosis orspinocerebellar degeneration), epilepsy, hepatic encephalopathy,peripheral neuropathy, Parkinson's syndrome, spasticity, pain,neuralgia, schizophrenia, anxiety, drug abuse, nausea, vomiting, urinarydisturbance, visual disturbance due to glaucoma, auditory disturbancedue to antibiotics, food poisoning, infectious cerebrospinal meningitis(such as HIV cerebrospinal meningtitis), cerebrovascular dementia, ordementia or nervous symptoms due to meningitis. Further, the compound ofthe present invention is useful as an agent for treating or preventingdemyelinating disorder (such as encephalitis, acute disseminatedencephalomyelitis, multiple sclerosis, acute demyelinatingpolyneuropathy, Guillain Barre syndrome, chronic inflammatorydemyelinating polyneuropathy, Marchifava-Bignami disease, centralpontine myelinolysis, neuromyelitis optica, Devic syndrome, Balodisease, HIV-myelopathy, HTLV-myelopathy, progressive multifocalleucoencephalopathy and a secondary demyelinating disorder (such as CNSlupus erythematodes, polyarteritis nodosa, Sjogren syndrome, sarcoidosisand isolated cerebral vasulitis)).

EXAMPLES

The following Reference Examples, Examples and Test Examples areexemplary, and not intended to limit the present invention. One skilledin the art may make various variations of Reference Examples, Examplesand Test Examples as well as claims of the invention to fully utilizethe invention. These variations shall be included in claims of theinvention.

Referential Example 1 5-Bromo-3-iodo-1,2-dihydropyridin-2-one

2-Amino-5-bromopyridine (CAS No. 1072-97-5) (300 g) was dissolved in amixed solvent consisting of 1000 ml of acetic acid and 200 ml of water,30 ml of concentrated sulfuric acid were gradually dropped thereintounder stirring. Then, 79.1 g of periodic acid hydrate and 176 g ofiodine were added thereto, followed by stirring at 80° C. for 4 hours.To the reaction mixture were added periodic acid hydrate (40 g)andiodine (22 g), followed by further stirring at 80° C. for 2 hours.After cooling to room temperature, the reaction mixture was poured ontoice (3000 ml) and neutralized to pH 7.0 with 5N aqueous sodiumhydroxide. The resulting crystals were collected by filtration,dissolved in a mixed solvent of ethyl acetate/diethyl ether,successively washed with aqueous sodium thiosulfate, water, 1N aqueoussodium hydroxide and brine, and dried over anhydrous magnesium sulfate.Then, the solvent was evaporated, to give 392 g of2-amino-5-bromo-3-iodopyridine (yield: 76%).2-Amino-5-bromo-3-iodopyridine (100 g) was gradually added to 300 ml ofconcentrated sulfuric acid under ice-cooling. After the reaction mixturewas stirred at room temperature for 2 hours, it was ice-cooled again. 35g of sodium nitrite were gradually added thereto, followed by stirringat room temperature for 3 days and nights. The reaction solution waspoured onto ice (3000 ml) and neutralized to pH 4.0 with sodiumhydroxide. The resulting crystals were collected by filtration, washedwith water and warm air-dried at 60° C. for one day and night, to give102 g (quantitative) of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.60 (d, 1H), 8.14 (d, 1H).

Referential Example 2 5-Bromo-1-phenyl-3-iodo-1,2-dihydropyridin-2-one

5-Bromo-3-iodo-1,2-dihydropyridin-2-one (10.0 g) obtained in ReferentialExample 1, 10.0 g of phenylboronic acid and 8.1 g of copper acetate weresuspended in 500 ml of dichloromethane. 15 ml of triethylamine wereadded thereto, followed by stirring at room temperature for 5 days andnights. To the reaction solution were added 200 ml of water and 50 ml ofaqueous ammonia, followed by stirring vigorously. Then the insolublematters were filtered off through Celite, the filtrate was extractedwith dichloromethane, the extract was dried over anhydrous magnesiumsulfate. The solvent was evaporated, and the residue was recrystallizedfrom ethyl acetate/hexane, to give 6.54 g (yield: 52%) of the titlecompound.

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.34-7.38 (m, 2H), 7.44-7.52 (m, 3H),7.53 (d, 1H), 8.10 (d, 1H).

Referential Example 35-Bromo-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one

5-Bromo-1-phenyl-3-iodo-1,2-dihydropyridin-2-one (11.69 g) obtained inReferential Example 2, 8.0 g of 2-(2-cyanophenyl)-1,3,2-dioxaborinateand 16.0 g of cesium carbonate were suspended in 150 ml ofdimethylformamide. 3.0 g of tetrakistriphenylphosphine palladium wereadded thereto, followed by stirring at 80° C. in nitrogen atmosphere for2 hours. The reaction solution was poured into water, the mixture wasextracted with ethyl acetate, the extract was successively washed withwater and brine and dried over anhydrous magnesium sulfate. Then, thesolvent was evaporated, and the residue was purified by a silica gelcolumn chromatography (hexane/ethyl acetate system), followed byrecrystallizing from ethyl acetate/hexane, to give 5.67 g (yield: 52%)of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.42-7.54 (m, 6H), 7.61-7.65 (m, 4H),7.66 (d, 1H), 7.74-7.77 (m, 1H).

Referential Example 4 5-(2-Pyridyl)-1,2-dihydropyridin-2-one

2,5-Diboromopyridine [CAS No. 624-28-2] (400 g) was added to 3500 ml ofa 28% methanolic solution of sodium methoxide, the mixture was stirredat 60° C. for 3 hours and allowed to cool, the reaction solution waspoured into 3 liters of water, the mixture was extracted with 9000 ml ofdiethyl ether, the extract was washed with a saturated saline solutionfor three times and dried over anhydrous magnesium sulfate and thesolvent was evaporated in vacuo. The residue was dissolved in 2 litersof dimethylformamide, 900 g of tri-N-butyl-(2-pyridyl) tin [CAS No.59020-10-9] and 20 g of tetrakistriphenylphosphinepalladium and mixturewas stirred at 120° C. in a nitrogen atmosphere for 3 hours. Thereaction solution was allowed to cool and poured into 3 liters of water,the mixture was extracted with 10 liters of diethyl ether, the extractwas successively washed with a saturated sodium bicarbonate solution anda saturated saline solution and the solvent was evaporated in vacuo. A48% aqueous solution (800 ml) of hydrogen bromide was added to theresidue and the mixture was stirred at 110° C. for 3 hours. Afterallowing to cool, the reaction solution was washed with 3 liters ofdiethyl ether, poured into 2 liters of ice, adjusted to pH 11.0 with a5N sodium hydroxide solution and washed with 3 liters of diethyl etheragain. The aqueous layer was adjusted to pH 7.0 and extracted withdichloromethane. The crude crystals prepared by evaporating the solventin vauco were washed with a mixed solvent consisting of diethyl etherand hexane to give 201.5 g (yield: 69%) of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.72 (d, 1H), 7.20 (ddd, 1H), 7.50-7.54(m,1H), 7.73 (dt,1H), 8.12-8.15 (m,1H), 8.19 (dd,1H), 8.60-8.64 (m, 1H).

Referential Example 5 3-Bromo-5-(2-pyridyl)-1,2-dihydropyridin-2-one

5-(2-Pyridyl)-1,2-dihydropyridin-2-one (201.5 g) obtained in ReferentialExample 4 was dissolved in 1300 ml of dimethylformamide, 208.3 g ofN-bromosuccimide were added thereto and the mixture was stirred at roomtemperature for 2 hours. The reaction mixture was poured into 4 litersof ice water and the precipitate was filtered and dried with warm air at50° C. for two days and nights to give 230 g (yield: 79%) of the titlecompound.

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.21-7.26 (m, 1H), 7.52 (d, 1H), 7.75(dt, 1H), 8.21 (d, 1H), 8.61-8.64 (m, 1H), 8.67 (d, 1H).

Referential Example 63-Bromo-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

Dichloromethane (300 ml) was added to 18.75 g of3-bromo-5-(2-pyridyl)-1,2-dihydropyridin-2-one obtained in ReferentialExample 5 and 18.36 of 3-pyridineboronic acid, then 3.47 g ofdi-μ-hydroxo-bis[(N,N,N′,N′-tetramethylethylenediamine) copper(II)]chloride were added and the mixture was stirred in an oxygenatmosphere for 4 days and nights. The reaction solution was purified byan NH silica gel short column (eluted by ethyl acetate), the solvent wasevaporated in vacuo and the resulting crude crystals were washed withdiethyl ether to give 24.26 g (yield: 99%) of the title compound.

¹H-NMR (400 MHz, CDCl₃);δ(ppm) 7.23-7.26(m,1H), 7.47-7.51(m,1H),7.52-7.56(m,1H), 7.77 (dt, 1H), 7.87-7.91 (m, 1H), 8.19 (d, 1H), 8.53(d, 1H), 8.59-8.62 (m, 1H), 8.71-8.75 (m, 2H).

Referential Example 7 1-(2-Pyridyl)-1,2-dihydropyridin-2-one

25 ml of a dimethylformamide solution containing 4.00 g of2(1H)-pyridone and 8.00 g of 2-bromopyridine was incorporated with 3.80g of potassium carbonate and 0.51 g of cupurous iodide, followed bystirring at 120° C. for 2 hours. After the mixture was returned to roomtemperature, water was added thereto. The mixture was extracted withethyl acetate, and the ethyl acetate layer was washed with water andbrine, and then dried over magnesium sulfate. The solvent wasevaporated, and the residue was purified by silica gel chromatography(ethyl acetate/hexane=1:1), to give 1.58 g of the title compound as apale yellow wax.

¹H-NMR(400 MHz, CDCl₃);δ(ppm) 6.31(dt,1H), 6.67(d,1H), 7.33(ddd, 1H),7.40(ddd, 1H), 7.82-7.90(m, 2H), 7.96(dd, 1H), 8.57(dd, 1H).

Referential Example 8 1-(2-Pyridyl)-5-bromo-1,2-dihydropyridin-2-one

Under ice-cooling, 15 ml of a dimethylformamide solution containing 1.50g of 1-(2-pyridyl)-1,2-dihydropyridin-2-one was incorporated with 1.60 gof N-bromosuccinic acid imide. The mixture was stirred at roomtemperature for 2 hours, and then diluted with water and extracted withethyl acetate. The organic layer was washed with water and brine, andthen dried over magnesium sulfate. The solvent was evaporated, and theresidue was purified by silica gel chromatography (ethylacetate/hexane=1:3), to give 1.13 g of the title compound as a palebrown powder.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.57(d,1H), 7.34(ddd,1H), 7.42(dd,1H),7.85(dt,1H), 7.97(dd,1H), 8.10(d,1H), 8.57(dd,1H).

Referential Example 91-(2-Pyridyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

2.5 ml of a dimethylformamide solution containing 0.10 g of1-(2-Pyridyl)-5-bromo-1,2-dihydropyridin-2-one and 0.30 g of 2-tributylstannyl pyridine was incorporated with 0.05 g ofdichlorobistriphenylphosphine palladium, followed by stirring at 130° C.for 2 hours. The mixture was returned to room temperature, followed bydiluting with water and extracting with ethyl acetate. The organic layerwas washed with water and brine, and then dried over magnesium sulfate.The solvent was evaporated, and the residue was purified by silica gelchromatography (ethyl acetate), to give 0.076 g of the title compound asa pale yellow powder.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.77(d,1H), 7.22(dd,1H), 7.36(dd,1H),7.61(d,1H), 7.76(dt,1H), 7.87(dt,1H), 7.97(d, 1H), 8.12(dd,1H),8.60-8.65(m,2H), 8.67(d,1H).

Referential Example 101-(2-Pyridyl)-5-(2-pyridyl)-3-bromo-1,2-dihydropyridin-2-one

2 ml of a dimethylformamide solution containing 0.07 g of1-(2-pyridyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one was incorporatedwith 0.07 g of N-bromosuccinic acid imide, under stirring andice-cooling. After stirring the mixture at room temperature for 2 hours,it was diluted with water and extracted with ethyl acetate. The organiclayer was washed with water and brine, and then dried over magnesiumsulfate. The solvent was evaporated, and the residue was purified bysilica gel chromatography (ethyl acetate/hexane=3:1), to give 0.05 g ofthe title compound as a pale brown powder.

¹H-NMR(400 MHz, DMSO-d₆); δ(ppm) 7.33(ddd, 1H), 7.58(ddd, 1H),7.83-7.88(m, 2H), 7.97(dd, 1H), 8.07(dt, 1H), 8.59-8.62(m, 1H)8.65-8.80(m, 1H), 8.72(d, 1H), 8.81(d, 1H).

Referential Example 11 3,5-Dibromo-2-methoxypyridine

80 ml of a 28% sodium methoxide solution was incorporated with 30.0 g of2,3,5-tribromopyridine under ice-cooling, followed by stirring at 50° C.for 2 hours. The reaction solution was diluted with water and extractedwith diethyl ether. The organic layer was washed with brine, and thendried over anhydrous magnesium sulfate. The solvent was evaporated, andthe residue was purified by silica gel chromatography (ethylacetate/hexane=1:20), to give 18.5 g of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.99(s,3H), 7.93(d, 1H), 8.14(d,1H).

Referential Example 12 3-(2-Pyridyl)-5-bromo-2-methoxypyridine

100 ml of a dimethylformamide solution containing 6.3 g of3,5-dibromo-2-methoxypyridine and 8.1 g of 2-tributyl stannyl pyridinewas incorporated with 1.0 g of tetrakistriphenylphosphine palladium,followed by stirring at 120° C. for 2 hours in nitrogen atmosphere.After the mixture was returned to room temperature, the solvent wasevaporated, and the residue was extracted with ethyl acetate. Theorganic layer was washed with water and brine, and then dried overmagnesium sulfate. The solvent was evaporated, and the residue waspurified by silica gel chromatography (ethyl acetate/hexane=1:3), togive 2.8 g of the title compound as a pale yellow powder.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 4.02(s, 3H), 7.31(dd,1H), 7.80(dt,1H),8.02(ddd,1H), 8.25(d,1H), 8.40(d,1H), 8.71-8.74(m,1H).

Referential Example 13 3-(2-Pyridyl)-5-phenyl-2-(1H)-pyridone

A mixture of 1.0 g of 3-(2-pyridyl)-5-bromo-2-methoxypyridine, 0.9 g ofphenylboronic acid, 0.3 g of dichlorobistriphenylphosphine palladium and2 ml of triethylamine was stirred at 120° C. for 1.5 hours in 30 ml ofxylene in nitrogen atmosphere. The mixture was returned to roomtemperature, diluted with ethyl acetate, washed with water and brine,and dried over magnesium sulfate. The solvent was evaporated, and theresidue was incorporated with 47% hydrobromic acid and heated at 70° C.for 1 hour. The reaction solution was ice-cooled, diluted with water,and neutralized with potassium carbonate. The resulting precipitateswere collected by filtration, washed with water and ether, and thenair-dried, to give 0.5 g of the title compound as a pale yellow powder.

¹H-NMR(400 MHz, DMSO-d₆); δ(ppm) 7.30-7.37(m, 2H), 7.43(dd, 2H), 7.62(d,2H), 7.82-7.90(m, 1H), 7.87(d, 1H), 8.64-8.69(m, 2H), 8.57(d, 1H),12.30(brs, 1H).

Referential Example 141-Phenyl-3-nitro-5-(2-pyridyl)-1,2-dihydropyridin-2-one

(14a) 3-Nitro-1-phenyl-1,2-dihydropyridin-2-one

5 g of 2-hydroxy-3-nitropyridine, 7.14 g of phenylboronic acid, 2.6 g ofcopper (II) acetate, 9.9 ml of triethylamine and 5.8 ml of pyridine wereadded to 100 ml of tetrahydrofuran, followed by stirring overnight. Thereaction mixture was poured into aqueous ammonia, and extracted withethyl acetate. The organic layer was washed with water, dried, andconcentrated. The residue was suspended into ether, and collected byfiltration, to give 4.71 g of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.39(dd, 1H), 7.36-7.40(m, 2H),7.49-7.54(m, 3H), 7.73(dd, 1H), 8.38(dd, 1H).

(14b) 5-Bromo-3-nitro-1-phenyl-1,2-dihydropyridin-2-one

10 ml of a dimethylformamide solution containing 1 g of3-nitro-1-phenyl-1,2-dihydropyridin-2-one was incorporated with 988 mgof N-bromosuccinimide, followed by stirring at room temperatureovernight. Further, it was stirred at 50° C. for 3 hours. The reactionmixture was poured into ice-water, and the resulting precipitates werecollected by filtration, to give 1.27 g of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.36-7.39(m,2H), 7.50-7.57(m,3H) 7.88(d,1H), 8.42(d, 1H).

(14c)

3-Nitro-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

1.27 g of 5-bromo-3-nitro-1-phenyl-1,2-dihydropyridin-2-one, 2.38 g of2-tri-n-butyl stannyl pyridine and 248 mg of tetrakistriphenylphosphinepalladium were added to 20 ml of xylene, followed by stirring at 120° C.overnight in nitrogen atmosphere. The reaction mixture was purified bysilica gel chromatography (ethyl acetate/hexane system), to give 638 mgof the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.28(ddd, 1H), 7.45-7.63(m, 6H),7.80(dt, 1H), 8.61(ddd, 1H), 8.63(d, 1H), 9.03(d, 1H).

Referential Example 153-Amino-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

100 mg of 10% palladium-carbon was added to 20 ml of an ethanol solutioncontaining 546 mg of3-nitro-1-phenyl-5-(pyridin-2-yl)-1,2-dihydropyridin-2-one, followed bystirring overnight in hydrogen atmosphere. The reaction mixture wasfiltered through silica gel and concentrated, to give 411 mg of thetitle compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 4.36-4.42(m, 1H), 7.18(dd, 1H), 7.28(d,1H), 7.44-7.54(m, 6H), 7.61(d, 1H), 7.70(dt, 1H), 8.57-8.60(m, 1H).

Referential Example 163-(2-Cyanophenyl)-5-(methoxycarbonyl)-1-phenyl-1,2-dihydropyridin-2-one

6 g of methyl 5-bromo-6-hydroxynicotinate synthesized by a known methodfrom 6-hydroxynicotinic acid, and 6.3 g of phenylboronic acid weredissolved in 200 ml of tetrahydrofuran. To the mixture were added 939 mgof copper acetate and 1 ml of pyridine, followed by stirring at roomtemperature for 3 nights. Aqueous ammonia was added to the reactionsolution, and the solution was extracted with chloroform. The organiclayer was washed with brine, and then dried over anhydrous magnesiumsulfate. The solvent was evaporated, and the residue obtained as a solidwas washed with diethyl ether, to give 7.35 g of3-bromo-5-(methoxycarbonyl)-1-phenyl-1,2-dihydropyridin-2-one as whitcrystals. 5 g of the product was dissolved in 100 ml ofdimethylformamide, followed by adding 4.6 g of2-(2-cyanophenyl)-1,3,2-dioxaborinate, 7.9 g of cesium carbonate and 375mg of tetrakistriphenylphosphine palladium, and stirring at 140° C. for1 hour in nitrogen atmosphere. After cooling to room temperature, thereaction mixture was poured into water, and extracted with ethylacetate. Then, the extract was successively washed with water and brine,and dried over anhydrous magnesium sulfate. Then, the solvent wasevaporated, and the residue was purified by silica gel chromatography(hexane/ethyl acetate system), to give 3.23 g of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.89(s, 3H), 7.42-7.55(m, 6H),7.61-7.66(m, 2H), 7.75(dd, 1H), 8.14(d, 1H), 8.35(d, 1H).

Referential Example 173-(2-Chlorophenyl)-5-hydroxymethyl-1-phenyl-1,2-dihydropyridin-2-one

36 mg of3-(2-chlorophenyl)-5-methoxycarbonyl-1-phenyl-1,2-dihydropyridin-2-onesynthesized by the method of Referential Example 3 from3-bromo-5-methoxycarbonyl-1-phenyl-1,2-dihydropyridin-2-one and2-chloroboronic acid, was dissolved in 20 ml of toluene. After coolingto −78° C., 0.1 ml diisopropyl aluminumhydride (1.5M tetrahydrofuransolution) was added dropwise thereinto. While heating from −78° C. toroom temperature, the mixture was stirred overnight. Then, 1Nhydrochloric acid was added thereto, followed by stirring. The mixturewas neutralized with an aqueous solution of sodium hydrogen carbonate,and then extracted with ethyl acetate. Then, the extract wassuccessively washed with water and brine, and dried over anhydrousmagnesium sulfate. Then, the solvent was evaporated, and the residue waspurified by silica gel chromatography (hexane/ethyl acetate system), togive 12 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 4.48 (s, 2H), 7.25-7.29 (m, 3H),7.37-7.51 (m, 8H).

ESI-Mass; 312 [M⁺+H]

Referential Example 183-Methoxycarbonyl-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

4.5 g of methyl 5-bromo-2-hydroxynicotinate synthesized by a knownmethod from 2-hydroxynicotinic acid, and 4.7 g of phenylboronic acidwere dissolved in 200 ml of tetrahydrofuran. To the mixture were added705 mg of copper acetate and 1 ml of pyridine, followed by stirring atroom temperature for 3 nights in a flow of air. Aqueous ammonia wasadded to the reaction solution, and the solution was extracted withchloroform. The organic layer was washed with brine, and dried overanhydrous magnesium sulfate. The solvent was evaporated, and the residueobtained as a solid was washed with diethyl ether, to obtain 3.59 g of5-bromo-3-methoxycarbonyl-1-phenyl-1,2-dihydropyridin-2-one as whitecrystals. 3.2 g of the product was dissolved in 100 ml ofdimethylformamide, to which 7.7 g of tri-N-butyl-(2-pyridyl)tin [CAS No.59020-10-9] and 240 mg of tetrakistriphenylphosphine palladium wereadded, followed by stirring at 110° C. for 3 hours in nitrogenatmosphere. After cooling to room temperature, the reaction solution waspoured into water, extracted with ethyl acetate. Then, the extract wassuccessively washed with water and brine, dried over anhydrous magnesiumsulfate, and then filtered through NH silica gel and silica gel. Then,the filtrate was evaporated, and the resulting precipitates were washedwith ether and hexane, and dried, to give 1.59 g of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.95(s, 3H), 7.22 (ddd, 1H), 7.42-7.54(m, 5H), 7.62 (dt, 1H), 7.76 (td, 1H), 8.52 (d, 1H), 8.58 (ddd, 1H),8.85 (d, 1H).

Referential Example 193-(2-Cyanophenyl)-5-nitro-1-phenyl-1,2-dihydropyridin-2-one

(19a) 5-Nitro-1-phenyl-1,2-dihydropyridin-2-one

5.93 g of the title compound was obtained in accordance with the methodused for Referential Example (14-1), from 5 g of2-hydroxy-5-nitropyridine.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.67(d, 1H), 7.39-7.43(m, 2H),7.53-7.59(m, 3H), 8.18(dd, 1H), 8.68(dd, 1H).

(19b) 3-Bromo-5-nitro-1-phenyl-1,2-dihydropyridin-2-one

4.72 g of the title compound was obtained in accordance with the methodused for Referential Example (14-2), from 5.93 g of5-nitro-1-phenyl-1,2-dihydropyridin-2-one.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.38-7.42(m, 2H), 7.54-7.58(m, 3H),8.59-8.61(m, 1H), 8.66-8.68(m, 1H).

(19c)

5-Nitro-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one

758 mg of the title compound was obtained in accordance with the methodused for Referential Example 3, from 3 g of3-bromo-5-nitro-1-phenyl-1,2-dihydropyridin-2-one.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.47-7.63(m, 7H), 7.68(dt, 1H),7.80(ddd, 1H), 8.38(d, 1H), 8.78(d, 1H).

Referential Example 205-Amino-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one

414 mg of the title compound was obtained in accordance with the methodused for Referential Example 15, from 708 mg of5-nitro-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.99(d, 1H), 7.39-7.49(m, 7H), 7.60(dt,1H), 7.73(d, 1H), 7.75(d, 1H).

Example 13-(2-Cyanophenyl)-5-(2-nitrophenyl)-1-phenyl-1,2-dihydropyridin-2-one

5-Bromo-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one (100 mg), 60mg of 2-nitrophenylboronic acid and 130 mg of cesium carbonate weresuspended in 10 ml of dimethylformamide, then 20 mg oftetrakistriphenylphosphine palladium were added and the mixture wasstirred at 120° C. in a nitrogen atmosphere for 4 hours. After allowingto cool, the reaction solution was poured into water, the mixture wasextracted with ethyl acetate, the extract was dried over anhydrousmagnesium sulfate, the solvent was evaporated in vacuo and the residuewas purified by a silica gel column chromatography (hexane-ethyl acetatesystem) to give 35 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.40-7.80 (m, 14H), 7.97 (dd, 1H).

Example 25-(2-Aminophenyl)-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one

3-(2-Cyanophenyl)-5-(2-nitrophenyl)-1-phenyl-1,2-dihydropyridin-2-one(32 mg) was dissolved in 15 ml of ethyl acetate, 5 mg of 10%palladium-carbon (water-containing substance) were added and the mixturewas stirred at room temperature in a hydrogen atmosphere for 15 minutes.The catalyst was filtered off and the solvent was evaporated in vacuo togive 20 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.95 (bs, 2H), 6.76 (dd, 1H), 6.80 (dt,1H), 7.14 (dd, 1H), 7.17 (dt, 1H), 7.41-7.55 (m, 6H), 7.59 (d, 1H), 7.62(dt, 1H), 7.74-7.82 (m, 2H), 7.88 (d, 1H).

Example 33-(2-Cyanophenyl)-5-(2-methylsulfonylaminophenyl)-1-phenyl-1,2-dihydropyridin-2-one

5-(2-Aminophenyl)-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one(16 mg) was dissolved in 10 ml of dimethylformamide, then 0.05 ml oftriethylamine and 3 drops of methanesulfonyl chloride were added and themixture was stirred at room temperature for one hour. Ethyl acetate wasadded to the reaction solution, the mixture was washed with water and asaturated saline solution, the solvent was evaporated in vacuo and theresidue was purified by a silica gel column chromatography (hexane-ethylacetate system) to give 5 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.19 (s, 3H), 6.88-6.95 (m, 1H),7.08-7.15(m,1H), 7.38-7.55(m,8H), 7.61(dt,1H), 7.69-7.76(m,3H), 7.91 (d,1H), 7.92-7.97 (m, 1H).

Example 43-(2-Chloro-3-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

3-Iodo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one (200 mg)synthesized by the same method as mentioned in Referential Example 6,130 mg of 2-chloro-3-pyridyl boronic acid and 250 mg of cesium carbonatewere suspended in 10 ml of dimethylformamide, 40 mg oftetrakistriphenylphosphine palladium were added and the mixture wasstirred at 100° C. in a nitrogen atmosphere for 3 hours. After allowingto cool, the reaction solution was poured into water, the mixture wasextracted with ethyl acetate, the extract was dried over anhydrousmagnesium sulfate, the solvent was evaporated in vacuo and the residuewas purified by a silica gel column chromatography (hexane-ethyl acetatesystem) to give 143 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.20-7.24 (m, 1H), 7.31 (dd, 1H),7.44-7.59 (m, 6H), 7.75 (dt, 1H), 7.91 (dd, 1H), 8.25 (d, 1H), 8.33 (d,1H), 8.41 (dd, 1H), 8.59-9.62 (m, 1H).

Example 5 3-(2-Cyanophenyl)-5-(2-pyridyl)-2-methoxypyridine

Tetrakistriphenylphosphine palladium (0.15 g) was added to a mixedsolution of 0.50 g of 5-(2-pyridyl)-3-bromo-2-methoxypyridine, 0.42 g of2-(2-cyanophenyl)-1,3,2-dioxaborinate, 0.82 g of cesium carbonate and 20ml of dimethylformamide and the mixture was stirred at 140° C. in anitrogen atmosphere for 5 hours. After cooling to room temperature,ethyl acetate was added thereto, the mixture was washed with water and asaturated saline solution and dried over magnesium sulfate. The solventwas concentrated in vacuo and the residue was purified by a silica gelcolumn chromatography (ethyl acetate:hexane=1:3) to give 0.36 of thetitle compound as pale yellow powder.

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 4.03 (3H, s), 7.24-7.28 (1H, m),7.46-7.51 (1H, ddd), 7.57 (1H, dd), 7.65-7.69 (1H, ddd), 7.72-7.82(3H,m), 8.31 (1H,d), 8.66-8.69 (1H,m), 8.83 (1H,d).

Example 6 3-(2-Cyanophenyl)-5-(2-pyridyl)-2(1H)-pyridone

Chlorotrimethylsilane (0.1 ml) was added to a suspension of 0.20 g of3-(2-cyanophenyl)-5-(2-pyridyl)-2-methoxypyridine and 0.12 g of sodiumiodide in 10 ml of acetonitrile and the mixture was stirred at roomtemperature for 3 hours. A saturated sodium bicarbonate solution wasadded to the mixture followed by extracting with ethyl acetate. Theethyl acetate layer was washed with water and a saturated salinesolution and dried over magnesium sulfate. The solvent was concentratedin vacuo and the residue was purified by a silica gel columnchromatography (ethyl acetate:hexane=1:1) to give 0.11 g of the titlecompound in pale yellow powder.

¹H-NMR (DMSO-d₆, 400 MHz); δ(ppm) 7.26-7.30(1H,ddd), 7.55-7.60(1H,ddd),7.66(1H,dd), 7.74-7.79(1H, ddd), 7.80-7.86(1H,ddd), 7.89-7.94(2H,m),8.28(1H,d), 8.37(1H,d), 8.56-8.59(1H,m).

Example 73-(2-Cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

A suspension of 0.11 g of3-(2-cyanophenyl)-5-(2-pyridyl)-2(1H)-pyridone, 0.12 g of phenyl boronicacid 0.1 g of copper acetate and 0.3 ml of triethylamine in 10 ml ofmethylene chloride was stirred at room temperature for overnight. Tothis were added 5 ml of concentrated aqueous ammonia, 10 ml of water and40 ml of ethyl acetate and the organic layer was separated, washed withwater and a saturated saline solution and dried over magnesium sulfate.The solvent was concentrated in vacuo and the residue was purified by asilica gel column chromatography (ethyl acetate:hexane=1:2) to give 0.06g of the title product as pale yellow powder.

¹H-NMR (DMSO-d₆, 400 MHz); δ(ppm) 7.29-7.33(1H,m), 7.48-7.63(6H,m),7.71-7.75(1H,dd), 7.76-7.88(2H,m), 7.92-7.95(1H,m), 8.01(1H,d),8.48(1H,d), 8.54(1H,d), 8.58-8.61(1H,m).

Example 83-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-nitrophenyl)-1,2-dihydropyridin-2-one

The title compound was obtained in the same manner as in Example 7.

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.24-7.28 (m, 1H), 7.49 (dt, 1H),7.63-7.81(m,6H), 7.95-7.98(m,1H), 8.31-8.37(m,3H), 8.45(t,1H),8.60-8.63(m,1H).

Example 93-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-aminophenyl)-1,2-dihydropyridin-2-one

Iron powder (180 mg) and 342 mg of ammonium chloride were added to asolution of 317 mg of3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-nitrophenyl)-1,2-dihydropyridin-2-onein a mixture of 10 ml of 2-propanol and 5 ml of water followed byrefluxing for 4 hours. The reaction mixture was concentrated,partitioned in ethyl acetate-water, the organic layer was washed withwater, dried and concentrated and the residue was purified by a silicagel column chromatography (ethyl acetate/hexane system) to give 235 mgof the title compound as a pale yellow solid.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.84 (s, 2H), 6.75 (dd, 1H),6.82-6.87(m,2H), 7.20 (dd,1H), 7.26-7.30 (m,1H), 7.45 (td,1H),7.59-7.65(m,2H), 7.72-7.80(m,3H), 8.29(s,2H), 8.56-8.61(m,1H)

Example 103-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-methylsulfonylaminophenyl)-1,2-dihydropyridin-2-one

Triethylamine (0.2 ml) was added to a solution of 31 mg of3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-aminophenyl)-1,2-dihydropyridin-2-onein 2 ml of tetrahydrofuran, 0.1 ml of methanesulfonic acid chloride wasdropped thereinto with ice cooling and the mixture was stirred for 10minutes. To this were added 2 ml of 2N sodium hydroxide, the mixture wasstirred at room temperature for 5 minutes and partitioned to ethylacetate-water, the organic layer was washed with water, dried andconcentrated and the residue was purified by a silica gel columnchromatography (ethyl acetate-hexane system) to give 38 mg of the titlecompound as a pale yellow amorphous substance.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.22-7.31 (m, 3H), 7.36 (t, 1H), 7.43(t,1H), 7.46 (dd,1H), 7.61 (dt,1H), 7.65 (td,1H), 7.73-7.78 (m,3H), 8.27(d, 1H), 8.31 (d, 1H), 8.59-8.61 (m, 1H).

Example 113-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-methylaminophenyl)-1,2-dihydropyridin-2-one

Paraformaldehyde (41 mg) and 119 mg of triacetoxy sodium borohydridewere added to a solution of 50 mg of3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-aminophenyl)-1,2-dihydropyridin-2-onein 3 ml of acetic acid followed by stirring at room temperature for onenight. To this was added an aqueous solution of sodium bicarbonate, themixture was extracted with ethyl acetate, the organic layer was washedwith water, dried and concentrated and the residue was purified by asilica gel column chromatography (ethyl acetate/hexane system) to give11 mg of the title compound as a pale yellow solid.

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 2.00 (s, 3H), 7.11-7.14 (m, 1H), 7.21(ddd, 1H), 7.35 (t, 1H), 7.44-7.49 (m, 2H), 7.59 (d, 1H), 7.66 (td, 1H),7.70-7.77 (m, 4H), 8.25 (d, 1H), 8.51 (s, 1H), 8.58-8.61 (m, 1H).

Example 123-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-dimethylaminophenyl)-1,2-dihydropyridin-2-one

Paraformaldehyde (41 mg) and 119 mg of triacetoxy sodium borohydridewere added to a solution of 50 mg of3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-aminophenyl)-1,2-dihydropyridin-2-onein 3 ml of acetic acid followed by stirring at room temperature for 6hours. To this were further added 41 mg of paraformaldehyde and 119 mgof triacetoxy sodium borohydride, the mixture was stirred for one night,an aqueous solution of sodium bicarbonate was added thereto, the mixturewas extracted with ethyl acetate, the organic layer was washed withwater, dried and concentrated and the residue was purified by a silicagel column chromatography (ethyl acetate/hexane system) to give 38 mg ofthe title compound as a pale yellow amorphous substance.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.99 (s, 6H), 6.77-6.80 (m, 3H),7.18-7.21(m,1H), 7.32-7.37(m,1H), 7.44(t,1H), 7.59-7.64(m,1H),7.71-7.83(m, 3H), 8.32 (s, 2H), 8.58-8.60 (m, 1H).

Example 133-(2-Cyanophenyl)-5-(2-pyridyl)-1-[3-(5-methoxymethyl-2-oxazolidinon-3-yl)-phenyl]-1,2-dihydropyridin-2-one

Glycidyl methyl ether (0.01 ml) and 22 mg of magnesium periodate wereadded to a solution of 38 mg of3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-aminophenyl)-1,2-dihydropyridin-2-onein 6 ml of acetonitrile followed by stirring at room temperature. After2 hours, 0.01 ml of glycidyl methyl ether and 22 mg of magnesiumperiodate were further added thereto and the mixture was stirred at roomtemperature for 1 hours and then stirred at 50° C. for 1 hour more. Thereaction mixture was partitioned to ethyl acetate-water, the organiclayer was washed with water, dried and concentrated, the residue wasdissolved in 6 ml of tetrahydrofuran, 32 mg of carbonyldiimidazole wereadded thereto and the mixture was heated to reflux for 2 hours. This waspartitioned to ethyl acetate-water, the organic layer was washed withwater, dried and concentrated and the residue was purified by apreparative thin layer chromatography (ethyl acetate/hexane system) togive 21 mg of the title compound as a pale yellow solid.

¹H-NMR (400 MHz, CDCl₃);δ(ppm) 3.43 (s,3H), 3.64 (dd,2H), 3.97(dd, 1H),4.09 (t, 1H), 4.77 (ddd, 1H), 7.22 (ddd, 1H), 7.29 (ddd, 1H), 7.46 (td,1H), 7.53 (t, 1H), 7.59-7.79 (m, 5H), 8.30 (d, 1H), 8.31 (d, 1H),8.58-8.61 (m, 1H).

Example 143-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-methoxycarbonylphenyl)-1,2-dihydropyridin-2-one

The title compound was obtained in the same manner as in Example 7.

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.94 (s, 3H), 7.23 (ddd, 1H), 7.47 (td,1H), 7.59-7.68 (m, 4H), 7.73-7.80 (m, 3H), 7.88-7.91 (m, 2H), 8.31 (d,1H), 8.32 (d, 1H), 8.59-8.61 (m, 1H).

Example 153-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-methylaminocarbonylphenyl)-1,2-dihydropyridin-2-one

3-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-methoxycarbonylphenyl)-1,2-dihydropyridin-2-one(10 mg) was added to 6 ml of a 40% methanolic solution of methylaminefollowed by stirring at room temperature for one night. The reactionsolution was concentrated in vacuo to give 10 mg of the title compoundas a pale yellow solid.

¹H-NMR (400 MHz, CDCl₃);δ(ppm) 3.00(d, 3H), 6.51(brs, 1H), 7.23 (ddd,1H), 7.47 (td, 1H), 7.58-7.68 (m, 4H), 7.73-7.80 (m, 3H), 7.88-7.91(m,2H), 8.31 (d, 1H), 8.32 (d, 1H), 8.59-8.61 (m, 1H).

Example 163-(2-Cyano-3-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

(Route 1)

3-(2-Chloro-3-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one(281 mg) was dissolved in 20 ml of dimethylformamide, 170 mg of coppercyanide were added and the mixture was stirred at 130° C. for 10 hours.The reaction solution was cooled to room temperature, aqueous ammoniaand ethyl acetate were added, the organic layer was partitioned, washedwith water and dried over anhydrous sodium sulfate, the drying agent wasfiltered off, the filtrate was concentrated in vacuo and the residue waspurified by a silica gel column chromatography (hexane-ethyl acetatesystem) to give 120 mg of the title compound as a colorless amorphoussubstance.

(Route 2)

3-Bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one (2.9 g)synthesized by the same method as mentioned in Referential Example 6 wasdissolved in 200 ml of xylene, 5 ml of bis(tributyl tin) and 400 mg oftetrakistriphenylphosphine palladium were added and the mixture wasstirred at 140° C. for 2 hours. 3-Bromo-2-cyanopyridine (3.2 g) and 100mg of tetrakistriphenylphosphine palladium were added thereto and themixture was stirred at 140° C. for 2 hours. Tetrakistriphenylphosphinepalladium (1.0 g) and 800 mg of copper iodide were divided into four andadded every 1 hour, then 2 g of 3-bromo-2-cyanopyridine were addedthereto and the mixture was stirred at 140° C. for one night. Thereaction solution was cooled to room temperature, water and ethylacetate were added thereto, the organic layer was partitioned, washedwith water and dried over anhydrous sodium sulfate, the drying agent wasfiltered off, the filtrate was concentrated in vacuo and the residue waspurified by a silica gel column chromatography (hexane-ethyl acetatesystem) to give 1.8 g of the title compound as a colorless amorphoussubstance.

¹H-NMR (400 MHz, CDCl₃);δ(ppm) 7.24 (ddd, 1H), 7.47-5.57 (m, 6H), 7.63(d, 1H), 7.68 (td, 1H), 8.22 (dd, 1H), 8.37 (dd, 1H), 8.43 (d, 1H),8.59-8.61 (m, 1H), 8.69 (dd, 1H).

ESI-Mass; 351 [M⁺+H]

Example 173-(2-Chlorophenyl)-5-(2-pyridyl)-1-(4-methoxyphenyl)-1,2-dihydropyridin-2-one

The title compound was obtained in the same manner as in Example 4.

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.84 (s, 3H), 6.98-7.03 (m, 2H), 7.19(ddd, 1H), 7.28-7.33 (m, 2H), 7.40-7.46 (m, 2H), 7.46-7.51 (m, 2H),7.53-7.57 (m, 1H), 7.72 (ddd, 1H), 8.12 (d, 1H), 8.29 (d, 1H), 8.57-8.61(m, 1H).

Example 183-(2-Chlorophenyl)-5-(2-pyridyl)-1-(4-hydroxyphenyl)-1,2-dihydropyridin-2-one

3-(2-Chlorophenyl)-5-(2-pyridyl)-1-(4-methoxyphenyl)-1,2-dihydropyridin-2-one(440 mg) was dissolved in 5 ml of 48% hydrobromic acid and heated toreflux for 1 hours. After the reaction solution was allowed to cool atroom temperature, it was diluted with a saturated aqueous solution ofsodium bicarbonate and extracted with ethyl acetate. The organic layerwas washed with water and dried over anhydrous magnesium sulfate. Thedrying agent was filtered off and the filtrate was concentrated in vacuoand purified by a silica gel column chromatography (hexane-ethyl acetatesystem) to give 292 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃);δ(ppm) 6.67-6.73(m,2H), 7.12-7.18(m,2H),7.19-7.24(m,1H), 7.30-7.38(m,2H), 7.47-7.53(m,2H), 7.56(d,1H), 7.70(s,1H), 7.73 (ddd,1H), 8.18 (d,1H), 8.26 (d,1H), 8.57-8.62 (m, 1H).

Example 193-(2-Chlorophenyl)-5-(2-pyridyl)-1-(4-dimethylaminoethoxyphenyl)-1,2-dihydropyridin-2-one

3-(2-Chlorophenyl)-5-(2-pyridyl)-1-(4-hydroxyphenyl)-1,2-dihydropyridin-2-one(82 mg) and 57 mg of N,N-dimethylaminoethyl chloride were dissolved in 2ml of dimethylformamide, 55 mg of potassium carbonate were added theretoat 60° C. and the mixture was stirred for one night. The reactionsolution was diluted with water and extracted with ethyl acetate. Theorganic layer was washed with a saturated saline solution and dried overanhydrous magnesium sulfate. The drying agent was filtered off and thefiltrate was concentrated in vacuo and purified by an NH silica gelcolumn chromatography (hexane-ethyl acetate system) to give 27 mg of thetitle compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.55 (s, 6H), 2.76 (t, 2H), 4.11 (t,2H), 6.99-7.05 (m, 2H), 7.19 (ddd, 1H), 7.26-7.34 (m, 2H),7.39-7.45(m,2H), 7.45-7.51(m,2H), 7.55(d,1H), 7.72(ddd,1H), 8.12 (d,1H), 8.28 (d, 1H), 8.57-8.61 (m, 1H).

Example 203-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-formylphenyl)-1,2-dihydropyridin-2-one

The title compound was obtained in the same manner as in Example 7.

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.24 (ddd, 1H), 7.84 (ddd, 1H), 7.63(d, 1H), 7.66 (ddd, 1H), 7.72 (dd, 1H), 7.75-7.82 (m, 3H), 7.84-7.88 (m,1H), 8.00 (ddd, 1H), 8.05-8.08 (m, 1H), 8.32 (d, 1H), 8.35 (d, 1H),8.59-8.62 (m, 1H), 10.08 (s, 1H).

Example 213-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-hydroxymethylphenyl)-1,2-dihydropyridin-2-one

3-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-formylphenyl)-1,2-dihydropyridin-2-one(585 mg) was dissolved in 20 ml of methanol, 260 mg of sodiumborohydride were added with ice cooling and the mixture was stirred atroom temperature for one night. The reaction solution was diluted withethyl acetate, washed with a saturated saline solution and dried overanhydrous magnesium sulfate. The drying agent was filtered off and thefiltrate was concentrated in vacuo and purified by an NH silica gelcolumn chromatography (ethyl acetate). The resulting crude crystals wererecrystallized from ethyl acetate-diethyl ether to give 320 mg of thetitle compound.

¹H-NMR (400 MHz, DMSO-d₆); δ(ppm) 4.60 (d, 2H), 5.37 (t, 1H), 7.29-7.33(m, 1H), 7.42-7.47 (m, 2H), 7.48-7.55 (m, 2H), 7.59 (ddd, 1H), 7.73 (dd,1H), 7.78 (dd, 1H), 7.83 (ddd, 1H), 7.94 (dd, 1H), 8.01 (d, 1H), 8.48(d, 1H), 8.52 (d, 1H), 8.57-8.61 (m, 1H).

Example 223-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-cyanomethylphenyl)-1,2-dihydropyridin-2-one

3-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-hydroxyphenyl)-1,2-dihydropyridin-2-one(53 mg) was dissolved in 2 ml of tetrahydrofuran, then 60 ml oftriethylamine and 20 ml of methanesulfonyl chloride were added theretowith ice cooling and the mixture was stirred at room temperature for 3hours. The reaction solution was diluted with an aqueous solution ofsodium bicarbonate and extracted with ethyl acetate and the extract wasdried over anhydrous magnesium sulfate. The drying agent was filteredoff, the filtrate was concentrated in vacuo, the resulting residue wasdissolved in 1 ml of dimethyl sulfoxide, 3 mg of sodium cyanide wereadded and the mixture was stirred at room temperature for 1 hour. Thereaction solution was diluted with ethyl acetate, washed with an aqueoussolution of sodium bicarbonate and a saturated saline solution and driedover anhydrous magnesium sulfate. The drying agent was filtered off, thefiltrate was concentrated in vacuo and the resulting crude crystals wererecrystallized from ethyl acetate-diethyl ether-hexane to give 12 mg ofthe title compound.

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.85 (s, 2H), 7.21-7.26 (m, 1H),7.41-7.81 (m, 10H), 8.29-8.32 (m, 2H), 8.59-8.62 (m, 1H).

The following compounds were prepared by the same manner as in the aboveExample 22.

Example 233-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-acetylaminomethylphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 2.04 (s, 3H) 4.47-4.52 (m, 2H), 7.22(ddd, 1H), 7.37-7.53 (m, 5H), 7.61 (d, 1H), 7.65 (ddd, 1H), 7.72-7.81(m, 3H), 8.28 (d, 1H), 8.31 (d, 1H), 8.59-8.62 (m, 1H).

Example 243-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-methylsulfonylaminomethylphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 2.91 (s, 3H), 4.36 (d, 2H), 5.00-5.06(m, 1H), 7.22 (ddd, 1H), 7.43-7.49 (m, 3H), 7.50-7.55 (m, 2H), 7.61(ddd, 1H), 7.64 (ddd, 1H), 7.73-7.79 (m, 3H), 8.28-8.31 (m, 2H), 8.60(ddd, 1H).

Example 253-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-acetoxymethylphenyl)-1,2-dihydropyridin-2-one

To 56 mg of3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-hydroxyphenyl)-1,2-dihydropyridin-2-onewere added 1 ml of acetic anhydride and 1 ml of pyridine and the mixturewas stirred at room temperature for one night. The reaction solution wasconcentrated in vacuo and purified by an NH silica gel chromatography(hexane-ethyl acetate system) to give 30 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 2.13(s,3H), 5.18(s,2H), 7.23(ddd,1H),7.44-7.56(m,5H), 7.60-7.67(m,2H), 7.73-7.81(m,3H), 8.30-8.33(m,2H),8.59-8.62(m,1H).

Example 263-(2-Cyanophenyl)-5-(2-pyridyl)-1-(4-methylthiophenyl)-1,2-dihydropyridin-2-one

The title compound was obtained in the same manner as in Example 7.

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 2.53 (s, 1H), 7.21-7.24 (m, 1H),7.36-8.79 (m, 10H), 8.28-8.32 (m, 2H), 8.59-8.61 (m, 1H).

Example 273-(2-Cyanophenyl)-5-(2-pyridyl)-1-(4-methylsulfonylphenyl)-1,2-dihydropyridin-2-one

A 70% m-chloroperbenzoic acid (500 mg) was added little by little during2 hours to a solution of 50 mg of3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-methylthiophenyl)-1,2-dihydropyridin-2-onein 4 ml of methylene chloride followed by stirring with ice cooling. Asaturated aqueous solution of sodium bicarbonate was added thereto, themixture was partitioned to ethyl acetate-water, the organic layer waswashed with water, dried and concentrated and the residue was purifiedby a silica gel column chromatography (ethyl acetate/hexane system) togive 5 mg of the title compound as a yellow solid.

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.11 (s, 3H), 7.24-7.28 (m, 1H),7.50(dt,1H), 7.61-7.82(m,7H), 8.20(d,2H), 8.30-8.33(m,2H),8.60-8.63(m,1H).

Example 283-(2-Cyanophenyl)-5-(2-formylthiophen-3-yl)-1-phenyl-1,2-dihydropyridin-2-one

The title compound was prepared according to Example 1.

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.29 (d, 1H), 7.42-7.57 (m, 6H), 7.65(dt, 1H), 7.71 (d, 1H), 7.77-7.82 (m, 3H), 7.85 (d, 1H), 10.10 (s, 1H).

Example 293-(2-Cyanophenyl)-5-(2-diethylaminomethylthiophen-3-yl)-1-phenyl-1,2-dihydropyridin-2-one

A solution of 20 mg of3-(2-cyanophenyl)-5-(2-formylthiophen-3-yl)-1-phenyl-1,2-dihydropyridin-2-one,0.1 ml of a 2M solution of diethylamine in tetrahydrofuran and 0.1 mlacetic acid in 2 ml of tetrahydrofuran was stirred at room temperaturefor 15 minutes, 20 mg of sodium triacetoxyborohydride were added and themixture was stirred for 3 hours more. A 2N aqueous solution of sodiumhydroxide was added thereto, the mixture was extracted with ethylacetate and the organic layer was washed with water and a saturatedsaline solution and dried over magnesium sulfate. The solvent wasconcentrated in vacuo and the residue was purified by an NH silica gelcolumn chromatography to give 15 mg of the title compound as whitepowder.

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 1.38 (t, 6H), 2.99-3.20 (m, 4H), 4.57(d,2H), 7.07 (d, 1H), 7.40-7.58 (m, 8H), 7.60-7.67 (m, 2H), 7.77 (d,1H), 7.87 (d, 1H).

Example 303-(2-Cyanophenyl)-5-(2-hydroxymethylthiophen-3-yl)-1-phenyl-1,2-dihydropyridin-2-one

Sodium triacetoxyborohydride (10 mg) was added to a solution of 10 mg of3-(2-cyanophenyl)-5-(2-formylthiophen-3-yl)-1-phenyl-1,2-dihydropyridin-2-onein 2 ml of tetrahydrofuran and the mixture was stirred for 1 hour. A 10%aqueous solution of sodium carbonate was added thereto, the mixture wasextracted with ethyl acetate and the organic layer was washed with waterand a saturated saline solution and dried over magnesium sulfate. Thesolvent was concentrated in vacuo and the residue was purified by an NHsilica gel column chromatography to give 8 mg of the title compound aswhite powder.

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 4.86(s, 2H), 7.11(d, 1H), 7.33(d, 1H),7.42-7.54(m, 6H), 7.60-7.65(m, 1H), 7.75(d, 1H), 7.76-7.79(m, 1H),7.81-7.84(m, 1H), 7.91(d, 1H).

MS (ESI): 385(MH⁺)

Example 313-(2-Cyanophenyl)-5-(2-pyridyl)-1-benzyl-1,2-dihydropyridin-2-one

3-(2-Cyanophenyl)-5-(2-pyridyl)-2(1H)-pyridone (46 mg), 36 mg of benzylalcohol and 88 mg of triphenylphosphine were dissolved in 2 ml oftetrahydrofuran, 147 mg of a 40% solution of diethylazo dicarboxylate intoluene were added with ice cooling and the mixture was stirred at roomtemperature for 1 hour. The reaction solution was concentrated in vacuoand purified by a silica gel chromatography (hexane-ethyl acetatesystem) to give 12 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 5.33 (s, 2H), 7.18 (ddd, 1H), 7.31-7.40(m,3H), 7.42-7.48 (m,3H), 7.53 (dd,1H), 7.64 (ddd,1H), 7.68-7.79 (m,3H),8.18 (d, 1H), 8.30 (d, 1H), 8.56-8.60 (m, 1H).

Example 323-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

3-Bromo-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one (5.39 g)was dissolved in 200 ml of dimethylformamide, then 6.42 g of cesiumcarbonate, 3.69 g of 2-(2′-cyanophenyl)-1,3,2-dioxaborian and 949 mg oftetrakistriphenylphosphinepalladium were added thereto and the mixturewas stirred at 120° C. for 1 hour. The reaction solution was cooled toroom temperature, water and ethyl acetate were added thereto, theorganic layer was partitioned, washed with water and dried overanhydrous magnesium sulfate, the drying agent was filtered off, thefiltrate was concentrated in vacuo and the residue was purified by asilica gel column chromatography (hexane-ethyl acetate system) to give4.8 g of the title compound as a colorless amorphous substance.

¹H-NMR (400 MHz, CDCl₃);δ (ppm) 7.22-7.26(m,1H), 7.46-7.52(m,2H),7.62(dt,1H), 7.66(td,1H), 7.74-7.81(m,3H), 7.97(ddd,1H), 8.32(s,2H),8.61(ddd,1H), 8.72(dd,1H), 8.80-8.81(m,1H).

ESI-Mass; 351 [M⁺+H]

The following compounds were synthesized by the same method as mentionedin Example 1.

Example 333-(2-Pyridyl)-5-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, DMSO-d₆); δ (ppm) 7.35-7.40 (1H, m), 7.49-7.64 (5H, m),7.77-7.81 (2H, m), 7.86 (1H, dt), 7.96 (1H, d), 8.22 (1H, d), 8.51 (1H,d), 8.66-8.71 (2H, m).

Example 343-(2-Cyanophenyl)-5-(3-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.38 (dd, 1H), 7.45-7.58 (m, 6H), 7.65(ddd, 1H), 7.72 (d, 1H), 7.77-7.86 (m, 3H), 7.94 (d, 1H), 8.60 (dd, 1H),8.79 (d, 1H).

Example 353-(2-Cyanophenyl)-5-(4-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.44 (dd,2H), 7.46-7.58(m,6H),7.66(ddd,1H), 7.81(dd,2H), 7.84(d,1H), 8.01(d,1H), 8.66(dd,2H).

Example 363-(2-Cyanophenyl)-5-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃);δ(ppm) 7.26-7.59(m,7H), 7.62-7.72(m,3H),7.76-7.80(m,2H), 7.82-7.84(m,1H), 7.86-7.88(m,2H).

ESI-Mass; 374 [M⁺+H]

Example 37 3,5-Diphenyl-1-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, DMSO-d₆); δ (ppm) 7.36-7.40 (3H, m), 7.41-7.47 (4H, m),7.52-7.56 (2H, m), 7.74-7.78 (2H, m), 7.84-7.90 (2H, m), 7.98-8.01 (1H,m), 8.11 (1H, d), 8.61-8.63 (1H, m).

Example 383-Phenyl-5-(2-cyanophenyl)-1-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, DMSO-d₆); δ (ppm) 7.34-7.40 (2H, m), 7.40-7.50 (3H, m),7.53 (2H, dd), 7.67 (1H, dt), 7.75-7.81 (2H, m), 7.83 (1H, d), 7.88 (1H,dt), 8.02 (1H, d), 8.15 (1H, d), 8.59-8.62 (1H, m).

Example 393-(2-Cyanophenyl)-5-phenyl-1-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, DMSO-d₆); δ (ppm) 7.33-7.40 (2H, m), 7.41-7.50 (3H, m),7.54-7.59 (2H, m), 7.65 (1H, dt), 7.75 (1H, dd), 7.80 (1H, dd), 7.88(1H, dt), 7.96 (1H, d), 8.03 (1H, d), 8.23 (1H, d), 8.60-8.64 (1H, m).

Example 403-(2-Cyanophenyl)-5-(2-cyanophenyl)-1-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, DMSO-d₆); δ (ppm) 7.36-7.40 (1H, m), 7.45-7.51 (2H, m),7.61-7.66 (1H, m), 7.66-7.71 (2H, m), 7.75-7.80 (3H, m), 7.86-7.91 (2H,m), 8.05-8.09 (1H, m), 8.34 (1H, d), 8.59-8.62 (1H, m).

Example 41 3-(2-Cyanophenyl)-1,5-diphenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.32-7.37 (m, 1H), 7.41-7.56 (m, 10H),7.63 (td, 1H), 7.69 (d, 1H), 7.77-7.82 (m, 2H), 7.98 (d, 1H).

ESI-Mass; 349 [M⁺+H]

Example 423-(2-Cyanophenyl)-5-(2-methoxyphenyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.88 (s, 3H), 6.95-7.04 (m, 3H),7.29-7.54(m,7H), 7.58-7.64(m,1H), 7.71(d,1H), 7.74-7.79 (m, 2H), 7.95(d, 1H).

Example 433-(2-Cyanophenyl)-5-(3,4-dimethoxyphenyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.91 (s, 3H), 3.94 (s, 3H), 6.92 (d,1H), 7.00-7.02 (m, 1H), 7.04 (dd, 1H), 7.40-7.59 (m, 6H), 7.60-7.68 (m,2H), 7.76-7.79 (m, 1H), 7.82-7.86 (m, 1H), 7.97 (d, 1H).

Example 443-(2-Cyanophenyl)-5-(thiophen-3-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.24 (dd, 1H), 7.35 (dd, 1H), 7.41 (dd,1H), 7.43-7.56 (m, 6H), 7.63 (dt, 1H), 7.70 (d, 1H), 7.76-7.81 (m, 2H),7.96 (d, 1H).

Example 453-(2-Cyanophenyl)-5-(2-fluorophenyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.16 (ddd, 1H), 7.23 (dt, 1H),7.29-7.36 (m, 1H), 7.42-7.54 (m, 6H), 7.60-7.67 (m, 2H), 7.74-7.81 (m,3H), 7.92 (dd, 1H).

Example 463-(2-Cyanophenyl)-5-(thiophen-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.07 (dd, 1H), 7.17 (dd, 1H), 7.25-7.28(m, 1H), 7.43-7.56 (m, 6H), 7.64 (dt, 1H), 7.72 (d, 1H), 7.74-7.80 (m,2H), 7.93 (d, 1H).

Example 473-(2-Cyanophenyl)-5-phenyl-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, DMSO-d₆); δ (ppm) 7.32-7.39 (1H, m), 7.41-7.47 (2H,m),7.52-7.65 (2H, m), 7.73-7.80 (4H, m), 7.94(1H, d), 8.06-8.11 (1H, m),8.20 (1H, d), 8.25 (1H, d), 8.68 (1H, dd), 8.83 (1H, d).

Example 483-(2-Cyanophenyl)-5-(3-furfuryl)-1-(phenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 6.55 (dd, 1H), 7.42-7.56 (m, 7H), 7.58(d, 1H), 7.60-7.67 (m, 2H), 7.74-7.79 (m, 2H), 7.82 (d, 1H).

Example 493-(2-Cyanophenyl)-5-(2-furfuryl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.12-7.24 (m, 2H), 7.42-7.55 (m, 6H),7.58-7.65 (m, 3H), 7.66(d, 1H), 7.74-7.77(m, 2H).

Example 503-(2-Cyanophenyl)-5-(2,4-dimethoxypyrimidin-5-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 4.03 (s, 3H), 4.07 (s, 3H) 7.42-7.57(m, 5H), 7.60-7.70 (m, 3H), 7.75-7.80 (m, 2H), 7.86 (d, 1H), 8.29 (s,1H).

Example 513-(2-Cyanophenyl)-5-(3-methoxypyridin-5-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.92 (s, 3H), 7.30-7.34 (m, 1H),7.44-7.58 (m, 6H), 7.65 (ddd, 1H), 7.72 (d, 1H), 7.77-7.84 (m, 2H), 7.95(d, 1H), 8.28-8.33 (m, 1H), 8.36-8.40 (m, 1H).

Example 523-(2-Cyanophenyl)-5-(2-methoxyphenyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.89(s,3H), 7.00(d,1H),7.03-7.08(ddd,1H), 7.35-7.40(m, 2H), 7.46-7.51(ddd, 1H), 7.63-7.72(m,2H), 7.72(d, 1H), 7.77-7.80(dd, 1H), 7.82-7.88(m, 1H), 7.95(d, 1H),8.47-8.52(d, 1H), 8.75-8.80(m, 1H), 8.96(brs, 1H).

Example 533-(2-Cyanophenyl)-5-[2-methoxy-5-(2-cyanophenyl)]-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.97(s, 3H), 7.12(d, 1H), 7.41-7.50(m,2H), 7.54-7.62(m, 3H), 7.62-7.68(ddd, 2H), 7.70-7.80(m, 4H), 8.03(d,1H), 8.32-8.38(m, 1H), 8.71-8.76(m, 1H), 8.93(brs, 1H).

Example 543-(2-Cyanophenyl)-5-(6-methyl-2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 2.56(s, 3H), 7.42-7.70(m, 10H),7.71-7.78(m, 2H), 7.89-7.93(m, 1H), 8.46-8.54(m, 1H).

The following compounds were synthesized by the method which is the sameas or according to the method mentioned in Example 4.

Example 553-(2-Methoxyphenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (DMSO-d₆, 400 MHz); δ (ppm) 3.76 (3H, s), 7.00 (1H, dt), 7.09(1H, d), 7.25-7.40 (3H, m), 7.46-7.60 (4H, m), 7.76-7.84 (2H, m), 7.94(1H, d), 8.23 (1H, d), 8.38 (1H, d), 8.55-8.58 (1H, m).

Example 563-(2-Methoxyphenyl)-5-(2-pyridyl)-1-(4-fluorophenyl)-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 3.82 (3H, s), 6.97-7.05 (2H, m),7.16-7.23 (2H, m), 7.24-7.32 (1H, m), 7.36 (1H, dt), 7.44 (1H, dd),7.50-7.66 (2H, m), 7.74-7.90 (1H, m), 8.02-8.08 (1H, m), 8.18-8.45(2H,m), 8.58-8.64(1H, m).

Example 573-(2-Chlorophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 6.76-6.81(2H,m), 6.86-6.91(1H,m),7.17-7.22 (2H, m), 7.26-7.75 (5H, m), 7.61 (1H, d), 7.78-7.86 (1H, m),8.11 (1H, d), 8.41 (1H, brs), 8.60-8.64 (1H, m).

Example 583-(2-Methoxycarbonylphenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (DMSO-d₆, 400 MHz); δ (ppm) 3.65 (3H, s), 7.28-7.32 (1H, m),7.47-7.71 (8H, m), 7.78-7.86 (2H, m), 8.01-8.20 (1H, m), 8.33 (1H, d),8.42 (1H, d), 8.58-8.60 (1H, m).

Example 593-(2-Methylaminocarbonylphenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (DMSO-d₆, 400 MHz); δ (ppm) 2.65 (3H, d), 7.26-7.31 (1H, m),7.40-7.45 (1H, m), 7.46-7.53 (5H, m), 7.53-7.59(2H, m), 7.80-7.86 (1H,m), 7.96 (1H, d), 8.06-8.12 (1H, m), 8.22 (1H, d), 8.37 (1H, d),8.57-8.60 (1H, m).

Example 60 3-(2-Tolyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (DMSO-d₆, 400 MHz); δ (ppm) 2.24 (3H, s), 7.22-7.34 (4H, m),7.47-7.60 (5H, m), 7.78-7.84 (1H, m), 7.99 (1H, d), 8.21-8.24 (1H, m),8.44-8.47 (1H, m), 8.55-8.59 (1H, m).

Example 61 3-Phenyl-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (DMSO-d₆, 400 MHz); δ (ppm) 7.28-7.32 (1H, m), 7.35-7.40 (1H, m),7.41-7.47 (2H, m), 7.49-7.54 (2H, m), 7.56-7.60 (3H, m), 7.76-7.86 (3H,m), 8.02 (1H, dd), 8.42 (1H, d), 8.44 (1H, d), 8.58-8.61 (1H, m).

Example 62 3-(2-Pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (DMSO-d₆, 400 MHz); δ (ppm) 7.29-7.40 (2H, m), 7.50-7.63 (5H, m),7.80-7.88 (2H, m), 7.99(1H, d), 8.50 (1H, d), 8.54 (1H, d), 8.62-8.66(1H, m), 8.70-8.74 (1H, m), 9.31 (1H, d).

Example 633-(3-Cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 7.24 (ddd, 1H), 7.46-7.66 (m, 8H), 7.78(td, 1H), 8.10 (dt, 1H), 8.16 (t, 1H), 8.25 (d, 1H), 8.31 (d, 1H),8.61-8.63 (m, 1H).

Example 643-(4-Cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 7.22-7.26 (m, 1H), 7.47-7.60 (m, 6H),7.70-7.78 (m, 3H), 7.95-7.98 (m, 2H), 8.26 (d, 1H), 8.33 (d, 1H),8.61-8.63 (m, 1H).

Example 653-(3-Chlorophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 7.21-7.36 (m, 3H), 7.47-7.76 (m, 5H),7.58-7.60 (m, 1H), 7.71-7.75 (m, 2H), 7.85 (m, 1H), 8.23-8.26 (m, 2H),8.60-8.63 (m, 1H).

ESI-Mass; 359 [M⁺+H]

Example 663-(4-Chlorophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 7.22 (ddd, 1H), 7.37-7.41 (m, 2H),7.44-7.60 (m, 5H), 7.72-7.80 (m, 3H), 8.12-8.16 (m, 1H), 8.21-8.25 (m,2H), 8.62 (ddd, 1H).

ESI-Mass; 359 [M⁺+H]

Example 67 3-(3-Pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 7.22-7.52 (m, 1H), 7.33-7.37 (m, 1H),7.45-7.57 (m, 5H), 7.59-7.61 (m, 1H), 7.56 (td, 1H), 8.24-8.27 (m, 2H),8.30 (d, 1H), 8.59 (dd, 1H), 8.61-8.63 (m, 1H), 8.95-8.96 (m, 1H).

ESI-Mass; 326 [M⁺+H]

Example 683-(2-Aminocarbonyl-3-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 5.46 (brs, 1H), 7.19 (ddd, 1H),7.39-7.53 (m, 6H), 7.55-7.58 (m, 1H), 7.58 (brs, 1H), 7.71 (ddd, 1H),7.82 (dd, 1H), 8.08 (d, 1H), 8.21 (d, 1H), 8.57 (dd, 1H), 8.59 (ddd,1H).

Example 693-(3-Methoxyphenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 3.84 (s, 3H), 6.92 (ddd, 1H), 7.20(ddd, 1H), 7.31-7.38 (m, 2H), 7.42-7.55 (m, 6H), 7.57-7.59 (m, 1H), 7.73(td, 1H), 8.23 (d, 1H), 8.24 (d, 1H), 8.60 (ddd, 1H).

ESI-Mass; 355 [M⁺+H]

Example 703-(4-Methoxyphenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 3.85 (s, 3H), 6.94-6.98 (m, 2H), 7.20(ddd, 1H), 7.42-7.55 (m, 5H), 7.57-7.60 (m, 1H), 7.73 (td, 1H),7.77-7.81 (m, 2H), 8.18-8.20 (m, 2H), 8.59-8.20 (m, 1H).

ESI-Mass; 355 [M⁺+H]

Example 713-(2-Fluorophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ(ppm) 7.13-7.22 (m, 3H), 7.31-7.59 (m, 7H),7.66 (td, 1H), 7.74 (td, 1H), 8.22 (dd, 1H), 8.29(d,1H), 8.58-8.60 (m,1H).

Example 723-(3-Fluorophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ(ppm) 7.03-7.08 (m, 1H), 7.21 (ddd,1H),7.35-7.63 (m, 9H), 7.74 (td, 1H), 8.23 (d, 1H), 8.27 (d, 1H), 8.59-8.62(m, 1H).

Example 733-(4-Fluorophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 7.08-7.14 (m, 2H), 7.21 (ddd, 1H),7.44-7.60 (m, 6H), 7.74 (td, 1H), 7.78-7.83 (m, 2H), 8.21 (d, 1H), 8.22(d, 1H) 8.60-8.62 (m, 1H).

Example 743-(2-Chlorophenyl)-5-(2-pyridyl)-1-(3-methoxyphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 3.84 (s, 3H), 6.96-7.01 (m, 1H),7.04-7.11 (m, 2H), 7.17-7.23 (m, 1H), 7.26-7.34 (m, 2H), 7.40 (dd, 1H),7.46-7.53 (m, 2H), 7.54-7.58 (m, 1H), 7.73 (ddd, 1H), 8.14 (d, 1H), 8.29(d, 1H), 8.57-8.62 (m, 1H).

Example 753-(2,4-Dimethoxyphenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 3.93 (s, 6H), 6.93 (d, 1H), 7.19-7.23(m, 1H), 7.33 (dd, 1H), 7.41-7.57 (m, 6H), 7.58-7.60 (m, 1H), 7.74 (td,1H), 8.19 (d, 1H), 8.22 (d, 1H), 8.60-8.62 (m, 1H).

ESI-Mass; 385 [M⁺+H]

Example 763-(2-Fluoro-3-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 7.20-7.28 (m, 2H), 7.44-7.56 (m, 5H),7.56-7.60 (m, 1H), 7.75 (td, 1H), 8.19-8.21 (m, 1H), 8.26 (ddd, 1H),8.30 (d, 1H), 8.34 (t, 1H), 8.59-8.61 (m, 1H)

ESI-Mass; 344 [M⁺+H]

Example 773-(4-Methoxy-3-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 3.98 (s, 3H), 6.80 (d, 1H), 7.22 (ddd,1H), 7.44-7.59 (m, 6H), 7.72-7.77 (m, 1H), 8.15 (dd, 1H), 8.21 (s, 2H),8.50-8.52(m, 1H), 8.59-8.62(m, 1H).

ESI-Mass; 356 [M⁺+H]

Example 783-(6-Cyano-2-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (DMSO-d₆, 400 MHz): δ (ppm) 7.30-7.34(ddd, 1H), 7.49-7.57(m, 1H),7.57-7.62(m, 4H), 7.62-7.66(dd, 1H), 7.82-7.87(ddd, 1H), 8.02(d, 1H),8.39-8.43(dd, 1H), 8.59-8.62(m, 1H), 8.63(d, 1H), 8.65(d, 1H),8.94-8.96(dd, 1H).

Example 793-(6-Cyano-2-pyridyl)-5-phenyl-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (DMSO-d₆, 400 MHz): δ (ppm) 7.33-7.38(m, 1H), 7.44(d, 1H),7.46(d, 1H), 7.64(d, 1H), 7.65(d, 1H), 7.72-7.76(dd, 2H), 8.07-8.11(m,1H), 8.30(d, 1H), 8.34(d, 1H), 8.42(dd, 1H), 8.68-8.71(dd, 1H),8.82-8.84(dd, 1H), 8.93-8.86(dd, 1H).

Example 803-(2-Fluoro-3-pyridyl)-5-(2-pyridyl)-1-(3-methoxyphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 3.85 (s, 3H), 6.99-7.10 (m, 3H),7.20-7.31(m,2H), 7.40-7.47(m,1H), 7.58(d,1H), 7.76(ddd,1H), 8.18-8.23(m, 1H), 8.23-8.32 (m, 2H), 8.32-8.37(m, 1H), 8.58-8.64(m,1H).

Example 813-(2-Methoxy-3-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 3.98 (s, 3H), 6.96 (dd, 1H), 7.18-7.22(m, 1H), 7.44-7.59 (m, 6H), 7.74(dt,1H), 7.90(dd,1H), 8.17 (dd, 1H),8.25-8.28 (m, 2H), 8.58-8.61 (m, 1H).

Example 823-(2-Fluoro-3-pyridyl)-5-(2-pyridyl)-1-(4-fluorophenyl)-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 7.18-7.30(m,4H), 7.46-7.52(m,2H),7.58(d, 1H), 7.76 (ddd, 1H), 8.20-8.27 (m, 2H), 8.29 (d,1H), 8.31-8.35(m, 1H), 8.59-8.64 (m, 1H).

Example 833-(2-Fluoro-3-pyridyl)-5-(2-pyridyl)-1-(pyrimidin-5-yl)-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 7.25-7.32 (m,2H), 7.61 (d, 1H),7.79(ddd,1H), 8.16-8.22(m,1H), 8.24-8.27(m,1H), 8.29(d,1H), 8.34-8.37(m, 1H), 8.61-8.64 (m, 1H), 9.01 (s, 2H), 9.32(s, 1H).

Example 843-(2-Fluoro-3-pyridyl)-5-(2-pyridyl)-1-(4-methylthiophenyl)-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 2.53 (s, 3H), 7.20-7.28 (m, 2H),7.36-7.43 (m, 4H), 7.57 (d, 1H), 7.75 (td,1H), 8.19-8.27(m, 2H), 8.28(d, 1H), 8.33 (t, 1H), 8.59-8.61(m, 1H).

ESI-Mass; 390 [M⁺+H]

Example 853-(2-Pyridon-5-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 6.67 (d, 1H), 7.21-7.26 (m, 1H),7.45-7.59 (m, 6H), 7.75 (td, 1H), 7.96 (dd, 1H), 8.14 (d, 1H), 8.26 (d,1H), 8.32 (m, 1H), 8.62 (m, 1H).

ESI-Mass; 342 [M⁺+H]

Example 863-(2-Fluoro-3-pyridyl)-5-(2-pyridyl)-1-(4-methoxy-3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 4.00 (s, 3H), 6.88 (dd, 1H), 7.22-7.29(m, 2H), 7.44-7.79 (m, 5H), 8.20-8.24(m, 1H), 8.27-8.29(m, 1H),8.33-8.36(m,1H), 8.61(ddd, 1H).

Example 873-(2-Fluoro-3-pyridyl)-5-phenyl-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (DMSO-d₆, 400 MHz): δ (ppm) 7.31-7.37(m,1H), 7.41-7.48(m, 2H),7.52-7.66(m, 2H), 7.71-7.76(d, 2H), 8.06-8.10(m, 1H), 8.16-8.28(m, 4H),8.66-8.70(dd, 1H), 8.80-8.82(d, 1H).

Example 883-(2-Fluoro-3-pyridyl)-5-(2-pyridyl)-1-(3-fluorophenyl)-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz); δ (ppm) 7.17-7.33 (m, 5H), 7.48-7.55 (m, 1H),7.56-7.61 (m, 1H), 7.76 (ddd, 1H), 8.20-8.27 (m, 2H), 8.29 (d, 1H),8.32-8.35 (m, 1H), 8.59-8.63 (m, 1H).

Example 893-(2-Dimethylamino-3-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (CDCl₃, 400 MHz): δ (ppm) 1.70(s, 6H), 7.19(ddd, 1H),7.41-7.60(m,7H), 7.71(td,1H), 7.82(d,1H), 8.08(d,1H), 8.21(d, 1H),8.57(dd, 1H), 8.58-8.60(m, 1H).

ESI-Mass; 369 [M⁺+H]

The following compounds were synthesized by the same method as mentionedin Example 7.

Example 90 3,5-Diphenyl-1-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR(400 MHz, CDCl₃); δ (ppm) 7.33-7.40(3H,m), 7.41-7.47(4H,m),7.54(2H, dd), 7.76(2H, dd), 7.86-7.90(2H, m), 7.99(1H, ddd), 8.11(1H,d), 8.61-8.64(1H, m).

Example 913-(2-Cyanophenyl)-5-(2-pyridyl)-1-(4-fluorophenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.18-7.25 (m, 3H), 7.44-7.55 (m, 3H),7.59-7.67 (m, 2H), 7.72-7.81 (m, 3H), 8.27-8.33 (m, 2H), 8.58-8.63 (m,1H).

Example 923-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-fluorophenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.15-7.25 (m, 2H), 7.28-7.36 (m, 2H),7.44-7.54 (m, 2H), 7.58-7.68 (m, 2H), 7.72-7.82 (m, 3H), 8.28-8.33 (m,2H), 8.57-8.63 (m, 1H).

Example 933-(2-Cyanophenyl)-5-(2-pyridyl)-1-(4-cyanophenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.23-7.26(m, 1H), 7.49 (dt, 1H),7.61-7.86 (m, 9H), 7.28-8.30 (m, 2H), 8.60-8.62 (m, 1H).

Example 943-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-cyanophenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.23-7.26(m, 1H), 7.49 (dt, 1H),7.61-7.89 (m, 9H), 8.30 (s, 2H), 8.60-8.62 (m, 1H).

Example 953-(2-Cyanophenyl)-5-(2-pyridyl)-1-(4-methoxyphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃);δ(ppm) 3.86 (s,3H), 7.02(d,2H), 7.21(ddd,1H),7.42-7.80(m,8H), 8.29(d,1H), 8.31(d,1H), 8.58-8.60(m,1H).

Example 963-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-methoxyphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.85 (s, 3H), 6.95-7.03 (m, 1H),7.06-7.10(m,2H), 7.20-7.22(m,1H), 7.41-7.81(m,7H), 8.31(s,2H), 8.59-8.61(m, 1H).

Example 973-Phenyl-5-(2-pyridyl)-1-(3-fluorophenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.15-7.24 (m, 2H), 7.26-7.33 (m, 2H),7.34-7.40 (m, 1H), 7.40-7.53 (m, 3H), 7.57-7.62(m, 1H), 7.72-7.82 (m,3H), 8.20-8.23 (m, 2H), 8.59-8.63 (m, 1H).

Example 983-Phenyl-5-(2-pyridyl)-1-(4-fluorophenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.18-7.24 (m, 3H), 7.34-7.39 (m, 1H),7.40-7.45 (m, 2H), 7.46-7.52 (m, 2H), 7.57-7.61 (m, 1H), 7.72-7.77 (m,1H), 7.77-7.82 (m, 2H), 8.19-8.23 (m, 2H), 8.59-8.62 (m, 1H).

Example 993-(2-Chlorophenyl)-5-(2-pyridyl)-1-(4-fluorophenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.16-7.24 (m, 3H), 7.29-7.35 (m, 2H),7.45-7.54(m,4H), 7.56(d,1H), 7.70-7.76(m,1H), 8.12 (d,1H), 8.28 (d, 1H),8.58-8.62 (m, 1H).

Example 1003-(2-Cyanophenyl)-5-(2-pyridyl)-1-(4-formylphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.22-7.27 (m, 1H), 7.48(ddd,1H),7.60-7.69 (m, 2H), 7.72-7.82 (m, 5H), 8.03-8.09 (m, 2H), 8.29 (d, 1H),8.33 (d, 1H), 8.58-8.62 (m, 1H), 10.10 (s, 1H).

Example 1013-(2-Cyanophenyl)-5-(2-pyridyl)-1-(2-formylphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.20-7.25 (m, 1H), 7.44-7.52 (m, 2H),7.61-7.70 (m, 3H), 7.73-7.83 (m, 4H), 8.06 (dd, 1H), 8.31 (d, 1H), 8.36(d, 1H), 8.57-8.60 (m, 1H), 10.05 (s, 1H).

Example 1023-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-chlorophenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.21-7.25 (m, 1H), 7.43-7.50 (m,4H),7.55-7.58 (m,1H), 7.59-7.68 (m,2H), 7.73-7.81(m,3H), 8.27-8.31 (m, 2H),8.58-8.62 (m, 1H).

Example 1033-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-tolyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 2.43 (s, 3H), 7.20-7.23 (m, 1H),7.26-7.35 (m, 3H), 7.39-7.48 (m, 2H), 7.60-7.66 (m, 2H), 7.72-7.81 (m,3H), 8.31 (s, 2H), 8.58-8.61 (m, 1H).

Example 1043-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-trifluoromethylphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.22-7.25 (m, 1H), 7.47 (t, 1H),7.61-7.82 (m, 9H), 8.31 (s, 2H), 8.59-8.62 (m, 1H).

Example 1053-(2-Cyanophenyl)-5-(2-pyridyl)-1-(thiophen-3-yl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.22-7.25 (m, 1H), 7.37-7.49 (m, 3H),7.59-7.67 (m, 3H), 7.74-7.80 (m, 3H), 8.27 (d, 1H), 8.40 (d, 1H),8.60-8.62 (m, 1H).

Example 1063-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-furfuryl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 6.83-6.86 (m, 1H), 7.19-7.26 (m, 1H),7.48 (ddd, 1H), 7.52 (dd, 1H), 7.60-7.69 (m, 2H), 7.73-7.82 (m,3H),8.21(d,1H), 8.27-8.30(m,1H), 8.47(d,1H), 8.61-8.65(m,1H).

Example 1073-(2-Cyanophenyl)-5-(2-pyridyl)-1-(4-tolyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 2.41 (s, 3H), 7.18-7.22 (m, 1H),7.30-7.46 (m, 5H), 7.59-7.65 (m, 2H), 7.71-7.80 (m, 3H), 8.29 (d,1H),8.31 (d, 1H), 8.58-8.60 (m, 1H).

Example 1083-(2-Cyanophenyl)-5-(2-pyridyl)-1-(4-trifluoromethylphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.22-7.25 (m, 1H), 7.48 (td, 1H),7.61-7.82 (m, 9H), 8.30 (d, 1H), 8.32 (d, 1H), 8.59-8.61 (m, 1H).

Example 1093-(2-Cyanophenyl)-5-(2-pyridyl)-1-(2-methoxypyridyn-5-yl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 4.00 (s, 3H), 6.88 (d, 1H), 7.23 (ddd,1H), 7.47 (td, 1H), 7.59-7.62 (m, 1H), 7.65 (td, 1H), 7.73-7.82 (m, 4H),8.28-8.31 (m, 3H), 8.60 (ddd, 1H).

ESI-Mass; 381 [M⁺+H]

Example 1103-(2-Cyanophenyl)-5-(2-pyridyl)-1-(2-cyanophenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.26-7.35 (m, 2H), 7.52-7.58 (m, 2H),7.64-7.71 (m, 2H), 7.72-7.85 (m, 5H), 8.51 (d, 1H), 8.68-8.72 (m, 1H),8.77 (d, 1H).

Example 1113-(2-Cyanophenyl)-5-(2-pyridyl)-1-(pyrimidin-5-yl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.24-7.32 (m, 1H), 7.48-7.54 (m, 1H),7.61-7.72 (m,2H), 7.73-7.85(m,3H), 8.31(d,1H), 8.33 (d,1H), 8.60-8.65(m, 1H), 9.04 (s, 2H), 9.32 (s, 1H).

Example 1123-(2-Cyanophenyl)-5-(2-pyridyl)-1-[2-(pyrrolidin-1-yl)-pyridin-5-yl]-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 2.01-2.07 (m, 4H), 3.49-3.52 (m, 4H),6.44 (dd, 1H), 7.21 (ddd, 1H), 7.45 (td, 1H), 7.58-7.67 (m, 3H), 7.72(dd, 1H), 7.76-7.88 (m, 2H), 8.23 (dd, 1H), 8.28 (dd, 2H), 8.59 (ddd,1H).

ESI-Mass; 420 [M⁺+H]

Example 1133-(2-Cyanophenyl)-5-(2-pyridyl)-1-[2-(4-benzylpiperazin-1-yl)-pyridin-5-yl]-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 2.57 (t, 4H), 3.63 (t, 4H), 3.57 (s,2H), 6.70 (d, 1H), 7.21 (ddd, 1H), 7.25-7.38 (m, 5H), 7.45 (td, 1H),7.58 (d, 1H), 7.63 (td, 1H), 7.68 (dd, 1H), 7.73(dd,1H), 7.75-7.79 (m,2H), 8.26-8.29 (m, 3H), 8.58-8.60 (m, 1H).

Example 1143-(2-Cyanophenyl)-5-(2-pyridyl)-1-(2-benzyloxyethoxypyridin-5-yl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃);δ(ppm) 3.84-3.87(m, 2H), 4.55-4.58(m, 2H), 4.64(s, 2H), 6.93 (d, 1H), 7.23 (ddd, 1H), 7.25-7.40 (m, 5H), 7.47 (td, 1H),7.60 (d, 1H), 7.65 (td, 1H), 7.74-7.82 (m, 4H), 8.27 (d, 1H), 8.28 (d,1H), 8.30 (d, 1H), 8.59-8.61 (m, 1H).

ESI-Mass; 501 [M⁺+H]

Example 1153-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-benzyloxymethylpyridin-5-yl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 4.64 (s, 2H), 4.66 (s, 2H), 7.23-7.26(m, 1H), 7.26-7.38 (m, 5H), 7.48 (td, 1H), 7.61 (d,1H), 7.68(td,1H),7.74-7.81(m,3H), 7.95-7.98 (m,1H), 8.29(d,1H), 8.32 (d,1H), 8.61 (d,1H), 8.69 (d, 1H), 8.72 (d, 1H).

ESI-Mass; 471 [M⁺+H]

Example 1163-(2-Cyanophenyl)-5-(2-pyridyl)-1-(2-ethylthiopyridin-5-yl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 1.41 (t, 3H), 3.23 (q, 2H), 7.23 (ddd,1H), 7.29 (dd, 1H), 7.47 (td, 1H), 7.60 (dt, 1H), 7.65 (td, 1H), 7.72(dd, 1H), 7.74-7.80 (m, 3H), 8.28 (d, 1H), 8.30 (d, 1H), 8.57 (dd, 1H),8.60 (ddd, 1H).

Example 1173-(2-Cyanophenyl)-5-(2-pyridyl)-1-(4-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.23-7.26 (m, 1H), 7.49 (td, 1H),7.55-7.57 (m, 2H), 7.61 (d, 1H), 7.67(td,1H), 7.73-7.81 (m, 3H), 8.29(d, 1H), 8.30 (d, 1H), 8.61 (ddd, 1H), 8.82 (d, 2H).

ESI-Mass; 351 [M⁺+H]

Example 1183-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-methoxypyridin-5-yl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.91 (s, 3H), 7.22-7.27 (m, 1H),7.46-7.51(m,2H) 7.60-7.64(m,1H), 7.66(ddd,1H), 7.74-7.82 (m,3H), 8.30(d, 1H), 8.32 (d, 1H), 8.38 (d, 1H), 8.43 (d, 1H), 8.60-8.63 (m, 1H).

Example 1193-(2-Cyanophenyl)-5-(2-pyridyl)-1-(2-hydroxyethoxypyridin-5-yl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.04 (brs, 1H), 3.97-4.03 (m, 2H),4.51-4.54 (m, 2H), 6.93 (d, 1H), 7.23 (dd, 1H), 7.47 (td, 1H), 7.61 (dd,1H), 7.65 (td, 1H), 7.74-7.80 (m, 3H), 7.84 (dd, 1H), 8.27-8.30 (m, 3H),8.61 (ddd, 1H).

ESI-Mass; 411 [M⁺+H]

Example 1203-(2-Cyanophenyl)-5-(2-pyridyl)-1-(2-chloropyridin-5-yl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.23-7.28 (m, 1H), 7.47-7.52 (m, 2H),7.61 (d, 1H), 7.67 (t, 1H), 7.72-7.81 (m, 3H), 7.95 (dd, 1H), 8.28 (d,1H), 8.30 (d, 1H), 8.59 (d, 1H), 8.61 (dt,1H).

ESI-Mass; 385 [M⁺+H]

Example 1213-(2-Cyanophenyl)-5-(2-pyridyl)-1-[2-(4-methylpiperazin-1-yl)-pyridin-5-yl]-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 2.37 (s, 3H), 2.54 (t, 4H), 3.66 (t,4H), 6.73(d, 1H), 7.21 (ddd,1H), 7.46 (td,1H), 7.59(d, 1H), 7.64(td,1H),7.70(dd,1H), 7.72-7.79(m, 3H), 8.27-8.29 (m, 3H), 8.58-8.60 (m, 1H).

ESI-Mass; 449 [M⁺+H]

Example 1223-(2-Cyanophenyl)-5-(2-pyridyl)-1-(3-tert-butyldimethylsilyloxymethylpyridin-5-yl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 0.13 (s, 6H), 0.95 (s, 9H), 4.85 (s,2H), 7.24 (dd, 1H), 7.45-7.81(m, 7H), 7.88 (s, 1H), 8.29 (d, 1H), 8.32(d, 1H), 8.61 (dd, 1H), 8.68 (d, 1H).

Example 1233-(2-Cyanophenyl)-5-(2-pyridyl)-1-(2-fluoropyridin-5-yl)-1,2-dihydropyridin-2-one

¹H-NMR(400 MHz, CDCl₃); δ (ppm) 7.11(dd, 1H), 7.25(ddd, 1H),7.42-7.84(m, 6H), 8.08(ddd, 1H), 8.30(t, 2H), 8.41(dd, 1H), 8.61(ddd,1H).

ESI-Mass; 369 [M⁺+H]

Example 1243-(2-Cyanophenyl)-5-(2-pyridyl)-1-(2-ethylpyridine-5-yl)-1,2-dihydropyridin-2-one

¹H-NMR(400 MHz, CDCl₃);δ(ppm) 1.36(t,3H), 2.91(q,2H), 7.23(m,1H),7.33(d,1H), 7.47(td,1H), 7.60(d,1H), 7.65(td,1H), 7.73-7.80(m,3H),7.86(dd,1H), 8.30(d,1H), 8.31(d,1H), 8.60(d,1H), 8.68(d,1H).

ESI-Mass; 379 [M⁺+H]

Example 1253-Phenyl-5-(2-pyridyl)-1-(2-cyanophenyl)-1,2-dihydropyridin-2-one

¹H-NMR (DMSO-d₆, 400 MHz); δ(ppm) 7.24-7.54(6H,m), 7.62-7.81(4H,m),7.93(1H,dt), 8.11(1H,d), 8.57(1H,d), 8.69-8.72(1H,m), 8.89-8.94(1H,m).

Example 1263-(2-Cyanophenyl)-5-(2-pyridyl)-1-(2-methoxyphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (DMSO-d₆, 400 MHz); δ (ppm) 3.80(3H,s), 7.12(1H,t),7.24-7.33(2H,m), 7.44(1H,dd), 7.49(1H,dt), 7.59(1H,dt), 7.71(1H,d),7.75-7.86(2H,m), 7.90-8.00(2H,m), 8.42(1H,d), 8.47(1H,d),8.56-8.60(1H,m).

The following compounds were synthesized by the same method as mentionedin Example 32.

Example 1273-Phenyl-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.23(ddd,1H), 7.36-7.50(m,4H),7.60(td,1H), 7.75(dd,1H), 7.76-7.80(m,2H), 7.94(ddd,1H), 8.22(d,1H),8.24(d,1H), 8.62(ddd,1H), 8.71(dd,1H), 8.75-8.79(m,1H).

ESI-Mass; 326 [M⁺+H]

Example 1283-(2-Chlorophenyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.23(ddd,1H), 7.31-7.36(m,2H),7.41-7.51(m,3H), 7.56-7.59(m,1H), 7.75(td,1H), 7.95(ddd,1H), 8.15(d,1H),8.30(d,1H), 8.60-8.62(m,1H), 8.69(dd,1H), 8.80(d,1H).

ESI-Mass; 360 [M⁺+H]

Example 129 3-(2-Methoxyphenyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.84(s,3H), 6.98-7.05(m,2H),7.21(ddd,1H), 7.37(td,1H), 7.41-7.49(m,2H), 7.56(d,1H), 7.74(td, 1H),7.94-7.97(m,1H), 8.13(d,1H), 8.25(d,1H), 8.58-8.60(m,1H), 8.67(dd, 1H),8.79(d, 1H).

ESI-Mass; 356 [M⁺+H]

Example 1303-(2-Formylthiophen-3-yl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.24-7.28(m,1H), 7.46-7.52(m,2H),7.57(d,1H), 7.50-7.79(m,2H), 7.92-7.96(m,1H), 8.24(d,1H), 8.30(d,1H),8.61-8.63(m,1H), 8.74(dd,1H), 8.79(d,1H), 9.99(d,1H).

Example 1313-(2,4-Dichlorophenyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.22-7.25(m,1H), 7.32(dd,1H),7.41-7.61(m,4H), 7.74-7.79(m,1H), 7.93-7.96(m,1H), 8.15(d,1H),8.29(d,1H), 8.59-8.63(m,1H), 8.69-8.72(m,1H), 8.79(d,1H).

ESI-Mass; 394 [M⁺+H]

Example 1323-(2-Trifluoromethylphenyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.22(ddd,1H), 7.44-7.56(m,4H),7.59-7.63(m,2H), 7.72-7.78(m,1H), 7.94(ddd,1H), 8.04(d,1H), 8.30(d,1H),8.59-8.61(m,1H), 8.69(dd,1H), 8.78-8.79(m,1H).

ESI-Mass; 394 [M⁺+H]

Example 1333-(Thiophen-3-yl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.24(ddd,1H), 7.39(dd,1H), 7.50(dd,1H),7.60-7.63(m,1H), 7.65(dd,1H), 7.77(td,1H), 7.93(ddd,1H), 8.15(d,1H),8.32(dd,1H), 8.44(d,1H), 8.62-8.64(m,1H), 8.72-8.73(m,1H), 8.77(d,1H).

ESI-Mass; 332 [M⁺+H]

Example 1343-(1-tert-Butoxycarbonylpyrrol-2-yl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 1.47(s,9H), 6.25(t,1H),6.36-6.34(m,1H), 7.21(dd,1H), 7.37(dd,1H), 7.43-7.48(m,1H), 7.57(d,1H),7.72-7.77(m,1H), 7.88-7.92(m,1H), 8.06(d,1H), 8.22(d,1H),8.59-8.61(m,1H), 8.68(dd,1H), 8.76(d,1H).

ESI-Mass; 415 [M⁺+H]

Example 1353-(2,6-Dimethylphenyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 2.23(s,6H), 7.11-7.27(m,3H),7.45-7.55(m,3H), 7.65-8.02(m,2H), 8.20-8.33(m,1H), 8.59-8.61(m,1H),8.68-8.81(m,3H).

ESI-Mass; 354 [M⁺+H]

Example 1363-(3-Acetylaminophenyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 2.08(s,3H), 7.21-7.26(m,1H),7.34(d,1H), 7.44-7.49(m,2H), 7.58-7.61(m,2H), 7.75(td,1H), 7.82(brs,1H),7.86(m,1H), 7.89-7.92(m,1H), 8.20-8.23(m,2H), 8.59-8.61(m,1H),8.69-8.71(m,1H), 8.77-8.78(m,1H).

ESI-Mass; 383 [M⁺+H]

Example 1373-(2-Cyanothiophen-3-yl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.23-7.26(m,1H), 7.50(dd,1H),7.61-7.74(m,3H), 7.79(td,1H), 7.91-7.94(m,1H), 8.36(d,1H), 8.57(d,1H),8.60-8.61(m,1H), 8.74(dd,1H), 8.79(d, 1H).

ESI-Mass; 357 [M⁺+H]

Example 1383-(2-Cyano-6-methoxyphenyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃): δ (ppm) 3.82(s,3H), 7.18-7.27(m,2H),7.35-7.38(dd,1H), 7.43-7.50(m,2H), 7.60(d,1H), 7.74-7.80(ddd,1H),7.98-8.02(m,1H), 8.16(d,1H), 8.35(d,1H), 8.59-8.62(m,1H),8.67-8.72(dd,1H), 8.83(d,1H).

Example 1393-(2-Fluoro-3-pyridyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 7.21-7.29(m,2H), 7.45-7.52(m,1H),7.59(d,1H), 7.78(dt,1H), 7.91-7.95(m,1H), 8.19-8.25(m,2H), 8.30(d,1H),8.35(t,1H), 8.60-8.63(m,1H), 8.70-8.73(m,1H), 8.79(d,1H).

The following compound was synthesized by the same method as mentionedin Example 15.

Example 1403-(2-Aminocarbonylphenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (DMSO-d₆, 400 MHz); δ (ppm) 7.17(1H,brs), 7.26-7.31(1H,m),7.40-7.64(10H,m), 7.82(1H,dt), 7.96(1H,d), 8.21(1H,d), 8.36(1H,d),8.56-8.59(1H,m).

The following compounds were synthesized by the same method as mentionedin Example 18.

Example 1413-(2-Hydroxyphenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (DMSO-d₆, 400 MHz); δ (ppm) 6.87-6.93(2H,m), 7.22(1H,dt)7.30(1H,ddd), 7.38(1H,dd), 7.48-7.60(5H,m), 7.82(1H,dt), 7.99(1H,d),8.41(1H,d), 8.45(1H,d), 8.57-8.60(1H,m), 9.43(1H,s).

Example 1423-(2-Hydroxyphenyl)-5-(2-pyridyl)-1-(4-fluorophenyl)-1,2-dihydropyridin-2-one

¹H-NMR (DMSO-d₆, 400 MHz); δ (ppm) 6.86-6.93(2H,m), 7.22(1H,dt),7.30(1H,ddd), 7.36-7.44(3H,m), 7.62-7.68(2H,m), 7.83(1H,dt), 7.98(1H,d),8.40(1H,d), 8.45(1H,d), 8.57-8.60(1H,m), 9.40(1H,s).

Example 1433-(2-Chlorophenyl)-5-(2-pyridyl)-1-(3-hydroxyphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 6.71-6.76(m,1H), 6.85-6.91(m,2H),7.19-7.34(m,4H), 7.41-7.50(m,2H), 7.56(d,1H), 7.74(ddd,1H), 8.17(d,1H),8.23(d,1H), 8.58-8.62(m,1H).

The following compounds were synthesized by the same method as mentionedin Example 19.

Example 1443-(2-Chlorophenyl)-5-(2-pyridyl)-1-(3-dimethylaminoethoxyphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 2.89(s,6H), 3.41(t,2H), 4.54(t,2H),6.99-7.04(m,1H), 7.13(dd,1H), 7.14-7.18(m,1H), 7.21(ddd,1H),7.30-7.35(m,2H), 7.43-7.51(m,3H), 7.58(d,1H), 7.74(ddd,1H), 8.15(d,1H),8.28(d,1H), 8.59-8.62(m,1H).

Example 1453-(2-Chlorophenyl)-5-(2-pyridyl)-1-(4-dimethylaminopropoxyphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 1.98(tt,2H), 2.26(s,6H), 2.46(t,2H),4.06(t,2H), 6.97-7.03(m,2H), 7.19(ddd,1H), 7.28-7.33(m,2H),7.39-7.44(m,2H), 7.46-7.51(m,2H), 7.53-7.58(m,1H), 7.72(ddd,1H),8.12(d,1H), 8.28(d,1H), 8.58-8.61(m,1H).

Example 1463-(2-Chlorophenyl)-5-(2-pyridyl)-1-(3-dimethylaminopropoxyphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 1.96(tt,2H), 2.25(s,6H), 2.44(t,2H),4.05(t,2H), 6.95-7.01(m,1H), 7.04-7.11(m,2H), 7.17-7.24(m,1H),7.28-7.35(m,2H), 7.36-7.43(m,1H), 7.45-7.53(m,2H), 7.56(d,1H),7.73(ddd,1H), 8.14(d,1H), 8.29(d,1H), 8.58-8.63(m,1H).

The following compounds were synthesized by the same method as mentionedin Example 21.

Example 1473-(2-Hydroxymethylphenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (DMSO-d₆; 400 MHz); δ (ppm) 4.46(2H,d), 5.04(1H,t),7.24-7.60(10H,m), 7.78-7.84(1H,m), 7.96-8.00(1H,m), 8.25(1H,d),8.45(1H,d), 8.55-8.59(1H,m).

Example 1483-(2-Cyanophenyl)-5-(2-pyridyl)-1-(4-hydroxymethylphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 1.81(t,1H), 4.78(d,2H),7.19-7.24(m,1H), 7.46(ddd,1H), 7.51-7.55(m,4H), 7.59-7.66(m,2H),7.72-7.80(m,3H), 8.28-8.32(m,2H), 8.58-8.61(m,1H).

Example 1493-(2-Cyanophenyl)-5-(2-pyridyl)-1-(2-hydroxymethylphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.35(dd,1H), 4.52(dd,1H), 4.62(dd,1H),7.21-7.24(m,1H), 7.35(dd,1H), 7.46-7.57(m,3H), 7.60-7.69(m,3H),7.72-7.81(m,3H), 8.26(d,1H), 8.36(d,1H), 8.58-8.62(m,1H).

The following compounds were synthesized by the same method as mentionedin Example 22.

Example 1503-(2-Cyanophenyl)-5-(2-pyridyl)-1-(4-cyanomethylphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.84(s,2H), 7.23(ddd,1H), 7.47(ddd,1H),7.49-7.54(m,2H), 7.55-7.63(m,3H), 7.65(ddd,1H), 7.73-7.81(m,3H),8.28-8.32(m,2H), 8.58-8.62(m,1H).

Example 1513-(2-Cyanophenyl)-5-(2-pyridyl)-1-(2-cyanomethylphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.81(d,1H), 3.91(d,1H), 7.24(ddd,1H),7.39-7.44(m,1H), 7.46-7.58(m,3H), 7.62(d,1H), 7.64-7.71(m,3H),7.73-7.81(m,2H), 8.22(d,1H), 8.34(d,1H), 8.59-8.63(m,1H).

The following compounds were synthesized by the same method as mentionedin Example 27.

Example 1523-(2-Cyanophenyl)-5-(2-pyridyl)-1-(2-ethylsulfonylpyridin-5-yl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 1.36(t,3H), 3.47(q,2H),7.26-7.29(m,1H), 7.51(td,1H), 7.63(d,1H), 7.68(td,1H), 7.71-7.82(m,3H),8.23-8.29(m,2H), 8.31-8.33(m,2H), 8.61-8.63(m,1H), 8.97-8.98(m,1H).

ESI-Mass; 443 [M⁺+H]

Example 1533-(2-Fluoro-3-pyridyl)-5-(2-pyridyl)-1-(4-methylsulfonylphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.11(s,3H), 7.24-7.30(m,2H),7.60(d,1H), 7.75-7.80(m,3H), 8.12(t,1H), 8.14(t,1H), 8.17-8.24(m,2H),8.30(d,1H), 8.35(t,1H), 8.61-8.63(m,1H).

ESI-Mass; 422 [M⁺+H]

The following compounds were synthesized by the same manner as mentionedin Example 29.

Example 1543-(2-Dimethylaminomethylphenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-onedihydrochloride

¹H-NMR (DMSO-d₆, 400 MHz); δ (ppm) 2.06(6H,s), 3.37(2H,s),7.25-7.39(4H,m), 7.44-7.61(6H,m), 7.81(1H,dt), 7.96(1H,d), 8.24(1H,d),8.43(1H,d), 8.55-8.58(1H,m).

Example 1553-(2-Cyanophenyl)-5-(2-pyridyl)-1-(2-dimethylaminomethylphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 2.16(s,6H), 3.30(d,1H), 3.46(d,1H),7.18-7.23(m,1H), 7.34-7.38(m,1H), 7.40-7.49(m,3H), 7.55-7.66(m,3H),7.70-7.79(m,3H), 8.21(d,1H), 8.37(d,1H), 8.58-8.61(m,1H).

Example 1563-(2-Cyanophenyl)-5-(2-pyridyl)-1-(4-dimethylaminomethylphenyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 2.28(s,6H), 3.49(s,2H), 7.22(ddd,1H),7.43-7.49(m,5H), 7.59-7.66(m,2H), 7.72-7.81(m,3H), 8.30(d,1H),8.33(d,1H), 8.58-8.61(m,1H).

Example 1573-(2-Cyanophenyl)-5-(6-diethylaminomethyl-2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 1.49(6H,t), 3.10-3.33(4H,m),4.36(2H,brs), 7.46-7.60(7H,m), 7.63-7.68(2H,m), 7.79-7.89(3H,m),8.28(1H,d), 8.39(1H,d).

The following compound was synthesized by the same method as mentionedin Example 31.

Example 1583-(2-Cyanophenyl)-5-(2-pyridyl)-1-phenethyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ (ppm) 3.18(t,2H), 4.33(t,2H), 7.19(ddd,1H),7.22-7.34(m,3H), 7.39(d,1H), 7.43-7.50(m,3H), 7.62-7.74(m,4H),7.96(d,1H), 8.18(d,1H), 8.56-8.60(m,1H).

Example 1593-(2-Cyanophenyl)-1-(2-pyridyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

A mixture of 0.05 g of1-(2-pyridyl)-S-(2-pyridyl)-3-bromo-1,2-dihydropyridin-2-one, 0.04 g of2-(2-cyanophenyl)-1,3,2-dioxaborinate, 0.02 g oftetrakistriphenylphosphine palladium and 0.1 g of cesium carbonate wasstirred at 120° C. in a nitrogen atmosphere for 2 hours indimethylformamide. The mixture was diluted with water, and extractedwith ethyl acetate. The organic layer was washed with water and thensaturated saline water, and dried by magnesium sulfate anhydride. Thesolvent was concentrated under a vacuum, and the residue was refined bysilica gel chromatography (ethyl acetate/hexane=3:1), to obtain 0.04 gof the white, powdery subject compound.

¹H-NMR (400 MHz, DMSO-d₆); δ (ppm) 7.33(dd, 1H), 7.56-7.64(m, 2H),7.75(d, 1H), 7.78-7.83(m, 1H), 7.84-7.90(m, 2H), 7.95(d, 1H),8.00(d,1H), 8.07(dt, 1H), 8.50(d, 1H), 8.61(d, 1H), 8.70(d, 1H), 8.83(d,1H).

Example 1601-(2-Cyanophenyl)-3-(2-pyridyl)-5-phenyl-1,2-dihydropyridin-2-one

5 ml of a dimethylformamide solution containing 0.26 g of3-(2-pyridyl)-5-phenyl-2(1H)-pyridone was incorporated with 0.04 g ofsodium hydride. After 15 minutes, the solution was further incorporatedwith 0.15 g of 2-fluorobenzonitrile and 0.10 g of cuprous iodide, andvigorously stirred at 100° C. for 2 hours. The solution was cooled toroom temperature, diluted with water, and extracted with ethyl acetate.The organic layer was washed with water and then saturated saline water,and dried by magnesium sulfate anhydride. The solvent was distilled offunder a vacuum. The residue was refined by silica gel chromatography(ethyl acetate/hexane=1:2), to obtain 0.03 g of the light yellow,powdery subject compound.

¹H-NMR (400 MHz, DMSO-d₆); δ (ppm) 7.34-7.42(m,2H), 7.45-7.50(m,2H),7.70-7.78(m, 3H), 7.84-7.90(m, 2H), 7.96(dt, 1H), 8.11(d, 1H), 8.31(d,1H), 8.47(dd, 1H), 8.71-8.74(m, 1H), 8.88(d, 1H).

Example 1611-Phenyl-3-(1-phenylacetylen-2-yl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

100 mg of 3-bromo-1-phenyl-5-(pyridin-2-yl)-1,2-dihydropyridin-2-one, 55mg of phenylacetylene, 1 mg of copper (I) iodide and 4 mg ofdichlorobis(triphenylphosphine) palladium were added to a mixed solventof 1.5 ml of triethylamine and 1 ml of dimethylformamide, and stirred at50° C. in a nitrogen atmosphere for a night. The reaction mixture wasdistributed into the ethyl acetate and water layers. The organic layerwas washed with water, dried and concentrated, and the residue wasrefined by silica gel chromatography (ethyl acetate/hexane-basedsolvent), to obtain 7 mg of the subject compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.22(dd, 1H), 7.33-7.35(m, 3H),7.46-7.60(m, 8H), 7.75(dt, 1H), 8.26(d, 1H), 8.34(d, 1H), 8.60(ddd, 1H).

Example 1625-(5-Acetoxypyridin-2-yl)-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one(162a) 3-(2-Cyanophenyl)-1-phenyl-5-(tri-n-butylstannyl)-1,2-dihydropyridin-2-one

5.50 g of 5-bromo-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one,45.5 g of bistributyl tin and 907 mg of tetrakistriphenylphosphinepalladium were added to 60 ml of xylene, and the mixture was stirred at120° C. in a nitrogen atmosphere for 40 minutes. The reaction mixturewas refined by silica gel chromatography (ethyl acetate/hexane-basedsolvent), to obtain 3.42 g of the subject compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 0.90(t, 9H), 1.07-1.11(m, 6H),1.30-1.39(m, 6H), 1.52-1.60(m, 6H), 7.29(d, 1H), 7.39-7.47(m,5H),7.49-7.52(m, 2H), 7.60(d, 1H), 7.71-7.75(m, 2H).

(162b)

5-(5-acetoxypyridin-2-yl)-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one

3.42 g of 3-(2-cyanophenyl)-1-phenyl-5-(tri-n-butylstannyl)-1,2-dihydropyridin-2-one, 1.57 g of 5-acetoxy-2-chloropyridineand 352 mg of tetrakistriphenylphosphine palladium were added to 40 mlof xylene, and the mixture was stirred at 120° C. in a nitrogenatmosphere for 8.5 hours. The reaction mixture was refined by silica gelchromatography (ethyl acetate/hexane-based solvent), to obtain 953 mg ofthe subject compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.36(s,3H), 7.44-7.56(m,6H),7.62-7.68(m,3H), 7.77-7.80(m,2H), 8.27(d,1H), 8.28(d,1H), 8.40(dd,1H).

Example 1633-(2-Cyanophenyl)-5-(5-hydroxypyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

953 mg of5-(5-acetoxypyridin-2-yl)-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-oneand 192 mg of potassium carbonate were added to 50 ml of methanol, andthe mixture was stirred at room temperature for 30 minutes. The mixturewas further incorporated with 50 ml of methanol, and stirred at 40° C.for 15 minutes. The reaction mixture was diluted with ethyl acetate, andfiltered by silica gel. The filtrate was concentrated under a vacuum andwashed with a ether/methanol-based solvent, to obtain 786 mg of thesubject compound.

¹H-NMR (400 MHz, DMSO-d₆); δ(ppm) 7.19(dd, 1H), 7.49-7.52(m, 1H),7.55-7.61(m, 5H), 7.71(dd, 1H), 7.78(dt, 1H), 7.82(d, 1H), 7.93(dd, 1H),8.14(d, 1H), 8.34(d, 1H), 8.37(d, 1H).

Example 1643-(2-Cyanophenyl)-1-phenyl-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one

63 mg of 2-tributyl tin pyrimidine, prepared in accordance withTetrahedron 50(1), 275, (1994), 50 mg of5-bromo-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one and 5 mgtetrakistriphenylphosphine palladium were added to 2 ml of xylene, andthe mixture was stirred at 120° C. in a nitrogen atmosphere for a night.The reaction mixture was refined by silica gel chromatography (ethylacetate/hexane-based solvent), to obtain 10 mg of the subject compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.15(t, 1H), 7.44-7.54(m, 6H),7.64(dt,1H), 7.72-7.78(m,2H), 8.70(s,1H), 8.71(s,1H), 8.72(d, 1H),8.76(d, 1H).

Example 1653-(2-Hydroxypyridin-6-yl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

20 mg of3-(2-methoxypyridin-6-yl)-1-phenyl-5-(pyridin-2-yl)-1,2-dihydropyridin-2-oneis added to 3 ml of 5N hydrochloric acid. The mixture was heated underreflux for 3 hours, to which 0.5 ml of concentrated hydrochloric acidwas added, and further stirred for 1 hour. The reaction mixture wasconcentrated under a vacuum and washed with ether, to quantitativelyobtain the subject compound.

¹H-NMR (400 MHz, DMSO-d₆); δ(ppm) 6.44(d, 1H), 7.08(brs, 1H), 7.47(dd,1H), 7.52-7.62(m, 6H), 8.02-8.06(m, 1H), 8.18(d, 1H), 8.62(d, 1H),8.68(dd, 1H), 8.82(dd, 1H).

Example 1661-(2-Aminobenzothiazol-6-yl)-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

150 mg of1-(3-aminophenyl)-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-oneand 63 mg of ammonium thiocyanate were added to 2 ml of acetic acid. Themixture was stirred at room temperature for 1 hour, to which 0.022 ml ofbromine was added, and further stirred for 1 hour. The reaction mixturewas distributed into the ethyl acetate and water layers, and neutralizedwith 20% aqueous solution of potassium carbonate. The organic layer waswashed with water, dried and concentrated, and the residue was refinedby silica gel chromatography (ethyl acetate/hexane-based solvent), toobtain 58 mg of the subject compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 5.37(brs, 1H), 6.76(d, 1H),7.20-7.24(m,1H), 7.41-7.80(m,8H), 8.28-9.40(m,2H), 8.59-8.61(m,1H).

Example 167 1,3-Diphenyl-4-methyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

The subject compound was obtained, at a yield of 27%, in accordance withthe method for Referential Examples 4, 5 and 6 and Example 32 from2,5-dibromo-4-methylpyridine.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.10(s, 3H), 7.27(ddd, 1H), 7.30-7.51(m,12H), 7.76(ddd, 1H), 8.66-8.70(m, 1H).

Example 1681-Phenyl-3-[N—(N′-phenylureylenyl)]-5-(2-pyridyl)-1,2-dihydropyridin-2-one

50 mg of 3-amino-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one and 25mg of phenyl isocyanate were dissolved in 1 ml of tetrahydrofuran, andthe solution was stirred at room temperature for 2 hours and at 60° C.for 2 hours. The reaction solution was left to cool to room temperature,to which diethyl ether was added. The resultant crystal was separated byfiltration, to obtain 30 mg of the subject compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.03-7.14(m,3H), 7.17-7.33(m,4H),7.38-7.44(m,2H), 7.45-7.50(m,2H), 7.59(br s,1H), 7.68-7.76(m,2H),8.02(d,1H), 8.54-8.57(m,1H), 8.58(br s,1H), 9.00(d,1H).

Example 1693-Benzoylamino-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

30 mg of 3-amino-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one wasdissolved in 1 ml of methylene chloride and 1 ml of pyridine, to which19 mg of benzoyl chloride was added with cooling with ice, and themixture was stirred at room temperature for a night. The reactionmixture was concentrated, diluted with ethyl acetate, and washed with asaturated aqueous solution of sodium bicarbonate. The organic layer wasdried by magnesium sulfate, and refined by NH silica gel chromatography(ethyl acetate). The solvent was concentrated, and the resultant crudecrystal was washed with ethyl acetate/hexane, to obtain 35 mg of thesubject compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.23(ddd, 1H), 7.47-7.60(m, 8H),7.70-7.80(m,2H), 7.95-8.00(m,2H), 8.12(d,1H), 8.57-8.61(m,1H),9.28(d,1H), 9.35(br s,1H).

Example 1703-Benzylamino-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

40 mg of 3-amino-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one and 10mg of sodium hydride were added to 1 ml of toluene, to which 30 mg ofbenzyl chloride was added dropwise at 70° C. The mixture was stirred for30 minutes, and heated for 1 hour under reflux. The reaction mixture wasleft to cool to room temperature, diluted with ethyl acetate, and washedwith a water and a saturated saline water. The organic layer was driedby magnesium sulfate, and refined by NH silica gel chromatography (ethylacetate/hexane-based solvent), to obtain 13 mg of the subject compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 4.48(d,2H), 5.60(brt,1H), 6.86(d, 1H),7.15(ddd, 1H), 7.26-7.32(m, 1H), 7.34-7.40(m, 2H), 7.40-7.56(m, 9H),7.66(ddd, 1H), 8.55-8.58(m, 1H).

Example 1713-(2-Cyanophenyl)-1-cyclopentyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

2.00 g of 3-bromo-5-(2-pyridyl)-1,2-dihydropyridin-2-one as the stockmaterial was N-alkylated by the normal method with 5.94 g ofbromocyclopentane and 5.50 g of potassium carbonate, to obtain 506 mg of3-bromo-1-cyclopentyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one, 150 mg ofwhich was treated in accordance with the method for Example 32, toobtain 120 mg of the subject compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.73-2.02(m,6H), 2.23-2.35(m,2H),5.37(quintet, 1H), 7.20(ddd, 1H), 7.45(ddd, 1H), 7.57(d, 1H), 7.64(ddd,1H), 7.70-7.79(m, 3H), 8.11(d, 1H), 8.36(d, 1H), 8.59-8.63(m, 1H).

Example 1721-{3-[1-(Benzyloxycarbonyl)piperidin-4-yl-oxy]phenyl}-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

0.99 g of3-bromo-1-(3-hydroxyphenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one wasobtained in accordance with the method for Example 18 from 1.02 g of3-bromo-1-(3-methoxyphenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one,synthesized in accordance with the method for Referential Example 6. Itwas dissolved 30 ml of tetrahydrofuran and 10 ml ofN,N-dimethylformamide, to which 1.52 g of triphenyl phosphine and 1.36 gof N-benzyloxycarbonyl-4-piperidinol were added, and further 2.52 g of a40% toluene solution of diethylazodicarboxylate was added dropwise withcooling with ice, and the mixture was stirred at room temperature for anight. The reaction solution was concentrated under a vacuum and refinedby silica gel chromatography (ethyl acetate/hexane-based solvent) toobtain 0.98 g of1-{3-[N-(benzyloxycarbonyl)piperidin-4-yl-oxy]phenyl}-3-bromo-5-(2-pyridyl)-1,2-dihydropyridin-2-one,from which 0.85 g of the subject compound was obtained in accordancewith the method for Example 32.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.73-1.87(m,2H), 1.88-2.02(m,2H),3.43-3.52(m,2H), 3.70-3.80(m,2H), 4.50-4.58(m,1H), 5.14(s,2H),6.98-7.02(m, 1H), 7.06-7.11(m, 2H), 7.22(dd, 1H), 7.30-7.38(m,5H),7.40-7.49(m,2H), 7.60(ddd,1H), 7.64(ddd,1H), 7.72-7.80(m, 3H), 8.29(d,1H), 8.31(d, 1H), 8.58-8.61(m, 1H).

Example 173 3-(2-Cyanophenyl)-5-(2-pyridyl1-oxide)-1-phenyl-1,2-dihydropyridin-2-one

1.00 g of3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one wasdissolved in 30 ml of chloroform, to which 0.99 g of 60%m-chloroperbenzoic acid was added, and the mixture was stirred at roomtemperature for 2 hours. Another 1.00 g of 60% m-chloroperbenzoic acidwas added to the mixture, and the mixture was stirred for 3 hours. Thereaction solution was incorporated with 50 ml of an aqueous solution of1N sodium hydroxide, and extracted with ethyl acetate. The organic layerwas washed with saturated saline water, dried by magnesium sulfateanhydride, and the solvent was distilled off under a vacuum. The residuewas recrystallized from ethyl acetate/diethyl ether, to obtain 0.46 g ofthe subject compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.21-7.27(m, 1H), 7.36(dt, 1H),7.43-7.48(m,2H), 7.50-7.54(m,4H), 7.61(dd,1H), 7.63(dt,1H), 7.78(dd,1H),7.81-7.85(m,1H), 8.10(d,1H), 8.21(dd,1H), 8.83(d, 1H).

Example 1743-Phenylamino-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

53 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one and 23mg of aniline were dissolved in 10 ml of toluene, to which 2 mg ofpalladium acetate, 7 mg of 1,1′-bis(diphenylphosphino)ferrocene and 23mg of sodium tert-butoxide were added, and the mixture was stirred at110° C. for a night. The reaction solution was cooled to roomtemperature, filtered by silica gel and washed with ether, and thefiltrate was distilled under a vacuum to remove the solvent. The residuewas refined by silica gel chromatography (NH silica) (hexane/ethylacetate-based solvent), to obtain 47 mg of the subject compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.06(tt, 1H), 7.15-7.19(m, 2H),7.29-7.31(m, 2H), 7.38(tt, 2H), 7.43-7.56(m, 5H), 7.67(d, 1H), 7.69(td,1H), 7.75(d, 1H), 8.58(ddd, 1H).

ESI-Mass; 340 [M⁺+H]

Example 175 3-Phenoxy-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

100 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one and 58mg of phenol were dissolved in 10 ml of dimethylformamide, to which 84mg of potassium carbonate and 6 mg of copper iodide were added, and themixture was stirred at 150° C. for 5 hours. The reaction solution wascooled to room temperature, to which ammonia water was added, andextracted with ethyl acetate. The organic layer was washed withsaturated saline water and dried by magnesium sulfate anhydride, and thesolvent was distilled off under a vacuum. The residue was refined bysilica gel chromatography (hexane/ethyl acetate-based solvent), toobtain 66 mg of the subject compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.13-7.19(m,3H), 7.26-7.27(m,2H),7.36-7.54(m,7H), 7.60-7.61(m,1H), 7.66-7.71(m,1H), 8.03-8.04(m,1H),8.54-8.57(m,1H).

ESI-Mass; 341 [M⁺+H]

Example 1763-(1-Adamantylamino)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

27 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one and 130mg of 1-adamantylamine were dissolved in 10 ml of dimethylformamide. Tothe mixture was added 20 mg of sodium hydride, followed by stirring at130° C. in nitrogen atmosphere. After the reaction solution was cooledto room temperature, a saturated aqueous solution of ammonium chlorideand water were added thereto, followed by extracting with ethyl acetate.The organic layer was washed with brine and dried over anhydrousmagnesium sulfate. The solvent was evaporated, and the residue waspurified by silica gel chromatography (hexane/ethyl acetate system), togive 3 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.19-2.29(m,16H), 7.06-7.33(m,3H),7.34-7.61(m,5H), 7.66-7.69(m,1H), 8.08-8.11(m,2H).

ESI-Mass; 398 [M⁺+H]

Example 1773-[4-(2-Cyanophenyl)piperadin-1-yl]-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

29 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one wasdissolved in 200 mg of 1-(2-cyanophenyl)piperazine, followed by heatingat 130° C. for 72 hours. After the reaction solution was cooled to roomtemperature, water was added thereto, followed by extracting with ethylacetate. The organic layer was washed with brine and dried overanhydrous magnesium sulfate. The solvent was evaporated, and the residuewas purified by silica gel chromatography (hexane/ethyl acetate system),to give 8 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.20-3.22(m,4H), 3.50-3.56(m,4H),7.00-7.13(m,3H), 7.32-7.61(m,10H), 7.79-7.84(m,2H).

ESI-Mass; 434 [M⁺+H]

Example 1783-(1-Adamantyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

40 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one wasdissolved in 10 ml of tetrahydrofuran. To the mixture were added 5 mg of[1,1-bis(diphenylphosphino)ferrocene]dichloropalladium (II) and 1.2 mgof copper (I) iodide. While stirring the mixture at room temperature innitrogen atmosphere overnight, 0.4 ml of 1-adamantyl zinc bromide (0.5Mtetrahydrofuran solution) was added dropwise thereinto. After stirringin nitrogen atmosphere overnight, an aqueous ammonia was added thereto,followed by extracting with ethyl acetate. The organic layer was washedwith brine and dried over anhydrous magnesium sulfate. The solvent wasevaporated, and the residue was purified by silica gel chromatography(hexane/ethyl acetate system), to give 12 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.44-2.19(m,15H), 7.13(ddd,1H),7.31-7.55(m,6H), 7.66(td,1H), 7.93(d,1H), 8.05(d,1H), 8.55-8.58(m,1H).

ESI-Mass; 383 [M⁺+H]

Example 1793-(1,1-Dichlorohexyl-1-hydroxymethyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

13 mg of3-methoxycarbonyl-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one wasdissolved in 20 ml of tetrahydrofuran, followed by the dropwise additionof 0.05 ml of cyclohexyl magnesiumchloride (2.0M diethyl ether solution)in nitrogen atmosphere, under ice-cooling and stirring. After themixture was stirred for 3 hr while heating to room temperature, asaturated aqueous solution of ammonium chloride was added thereto,followed by extracting with ethyl acetate. The organic layer was washedwith brine and dried over anhydrous magnesium sulfate. The solvent wasevaporated, and the residue was purified by silica gel chromatography(hexane/ethyl acetate system), to give 8 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 0.89-1.84(m,20H), 2.72-2.90(m,2H),7.12-7.06(m,1H), 7.25-7.49(m,8H), 7.59-7.68(m,1H), 8.50-8.54(m,1H).

ESI-Mass; 443 [M⁺+H]

Example 1803-(2-Cyanophenyl)-5-(2-pyridyl)-1-(1-benzyl-1,2,3,6-tetrahydropyridin-5-yl)-1,2-dihydropyridin-2-one

718 mg of 3-bromo-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-onewas dissolved in 40 ml of acetonitrile. 383 mg of benzyl bromide wasadded thereto, followed by stirring at 70° C. overnight. Further, 383 mgof benzyl bromide was added thereto, followed by stirring at 70° C. for2 nights. After cooling to room temperature, the mixture was evaporated.The residue was dissolved in 30 ml of methanol, followed by cooling to0° C. under stirring. 265 mg of sodium borohydride was added thereto,followed by stirring overnight under heating from 0° C. to roomtemperature. Water was added thereto, the solvent was evaporated, andthen the residue was extracted with ethyl acetate. The organic layer waswashed with brine and dried over anhydrous magnesium sulfate. Thesolvent was evaporated, and the residue was purified by silica gelchromatography (hexane/ethyl acetate system), to give 550 mg of3-bromo-5-(2-pyridyl)-1-(1-benzyl-1,2,3,6-tetrahydropyridin-5-yl)-1,2-dihydropyridin-2-one.270 mg of the product was dissolved in 20 ml of dimethylformamide. 179mg of 2-(2-cyanophenyl)-1,3,2-dioxaborinate, 313 mg of cesium carbonateand 15 mg of tetrakistriphenylphosphinepalladium were added thereto,followed by stirring at 120° C. for 1 hour. After cooling to roomtemperature, water was added thereto, followed by extracting with ethylacetate. The organic layer was washed with brine and dried overmagnesium sulfate. The solvent was evaporated, and the residue waspurified by silica gel chromatography (hexane/ethyl acetate system), togive 174 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.40(m,2H), 2.70(t,2H), 3.43(d,2H),3.68(s,2H), 6.05(t,1H), 7.21(dd,1H), 7.24(m, 1H), 7.30(t,2H),7.36(d,2H), 7.44(t,1H), 7.54(d,1H), 7.63(t, 1H), 7.70-7.77(m, 3H),8.19(d, 1H), 8.23(d, 1H), 8.60(dd, 1H).

Example 1813-(2-Cyanophenyl)-5-phenylaminocarbonyl-1-phenyl-1,2-dihydropyridin-2-one

41 mg of carboxylate obtained by hydrolyzing the ester group of3-(2-cyanophenyl)-5-(methoxycarbonyl)-1-phenyl-1,2-dihydropyridin-2-onewas dissolved in 5 ml of dichloromethane. Under ice-cooling, a solutionof 25 mg of oxalyl chloride in dichloromethane was added dropwisethereinto and a catalytic amount of dimethylformamide was added thereto,followed by stirring at room temperature in nitrogen atmosphere for 1hour. The reaction solution was evaporated, and the residue wasdissolved in dichloromethane. The solution was added dropwise into asolution of 13 mg of aniline and 0.03 ml of triethylamine indichloromethane under ice-cooling. After heating to room temperature, itwas stirred in nitrogen atmosphere for 3 hours. Under ice-cooling, themixture was poured into a saturated aqueous solution of sodium hydrogencarbonate, followed by extracting with ethyl acetate. The organic layerwas washed with brine, and then dried over anhydrous magnesium sulfate.The solvent was evaporated, and the residue was purified by silica gelchromatography (hexane/ethyl acetate system), to give 11 mg of the titlecompound as white crystals.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.15(tt, 1H), 7.33-7.39(m, 2H),7.55-7.42(m,6H), 7.56-7.60(m,2H), 7.65(td,1H), 7.73-7.79(m,2H),7.85(brs,1H), 8.06(d,1H), 8.25(d,1H).

Example 1823-(2-Cyanophenyl)-5-(1-phenylbenzimidazol-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

24 mg of carboxylate obtained by hydrolyzing the ester group of3-(2-cyanophenyl)-5-(methoxycarbonyl)-1-phenyl-1,2-dihydropyridin-2-onewas dissolved in 20 ml of dichloromethane. Under ice-cooling, a solutionof 16 mg of oxalyl chloride in dichloromethane was added dropwisethereinto. A catalytic amount of dimethylformamide was added thereto,followed by stirring at room temperature in nitrogen atmosphere for 1hour. The reaction solution was evaporated, and the residue wasdissolved in dichloromethane. The solution was added dropwise into asolution of 21 mg of N-phenyl-1,2-phenylenediamine in dichloromethane,under ice-cooling. The mixture was heated to room temperature, followedby stirring in nitrogen atmosphere overnight. Dichlotomethane wasevaporated, 10 ml of acetic acid was added, and the mixture was stirredat 100° C. for 5 hours. After cooling to room temperature, acetic acidwas evaporated. Under ice-cooling, the residue was poured into asaturated aqueous solution of sodium hydrogen carbonate, followed byextracting with ethyl acetate. The organic layer was washed with brineand dried over anhydrous magnesium sulfate. The solvent was evaporated,and the residue was purified by silica gel chromatography (hexane/ethylacetate system), to give 18 mg of the title compound as white crystals.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.19-7.30(m,4H), 7.33-7.37(m,1H),7.39-7.43(m,4H), 7.44-7.45(m,1H), 7.46-7.47(m,1H), 7.55-7.61(m,3H),7.61-7.66(m,2H), 7.68(d,1H), 7.71(dd,1H), 7.81-7.84(m,1H), 7.87(d,1H).

ESI-Mass; 465 [M⁺+H]

Example 1833-(2-Chlorophenyl)-5-(2-benzothiazolyl)-1-phenyl-1,2-dihydropyridin-2-one

19 mg of carboxylate obtained by hydrolyzing the ester group of3-(2-chlorophenyl)-5-(methoxycarbonyl)-1-phenyl-1,2-dihydropyridin-2-one(synthesized from3-bromo-5-(methoxycarbonyl)-1-phenyl-1,2-dihydropyridin-2-one and2-chlorophenylboronic acid in accordance with the method for ReferentialExample 3) was dissolved in 20 ml of dichloromethane. Under ice-cooling,a solution of 11 mg of oxalyl chloride in dichloromethane was addeddropwise thereinto and a catalytic amount of dimethylformamide was addedthereto, followed by stirring at room temperature in nitrogen atmospherefor 1 hour. The reaction solution was evaporated, and the residue wasdissolved in dichloromethane. The solution was added dropwise into asolution of 22 mg of 2-aminobenzothiol in dichloromethane underice-cooling. After heating to room temperature, dichloromethane wasevaporated. To the residue was added 1 ml of polyphosphoric acid,followed by stirring at 180° C. overnight. After cooling to roomtemperature, the reaction mixture was neutralized with 1N aqueoussolution of sodium hydroxide and saturated aqueous solution of sodiumhydrogen carbonate under ice-cooling and extracted with ethyl acetate.The organic layer was washed with brine and dried over anhydrousmagnesium sulfate. The solvent was evaporated, and the residue waspurified by silica gel chromatography (hexane/ethyl acetate system), togive 4 mg of the title compound as white crystals.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.32-7.35(m,2H), 7.37-7.41(m,1H),7.46-7.51(m,4H), 7.51-7.55(m,4H), 7.87-7.89(m,1H), 8.00(d,1H),8.14(d,1H), 8.42(d,1H).

ESI-Mass; 415 [M⁺+H]

Example 1843-(2-Chlorophenyl)-5-(2-benzoxazolyl)-1-phenyl-1,2-dihydropyridin-2-one

19 mg of carboxylate obtained by hydrolyzing the ester group of3-(2-chlorophenyl)-5-(methoxycarbonyl)-1-phenyl-1,2-dihydropyridin-2-one(synthesized from3-bromo-5-(methoxycarbonyl)-1-phenyl-1,2-dihydropyridin-2-one and2-chlorophenylboronic acid in accordance with the method of ReferentialExample 3) was dissolved in 20 ml of dichloromethane. Under ice-cooling,a solution of 11 mg of oxalyl chloride in dichloromethane was addeddropwise thereinto and a catalytic amount of dimethylformamide was addedthereto, followed by stirring at room temperature in nitrogen atmospherefor 1 hour. The reaction solution was evaporated, and the residue wasdissolved in dichloromethane. The solution was added dropwise into asolution of 19 mg of 2-aminophenol in dichloromethane under ice-cooling.After heating to room temperature, dichloromethane was evaporated. Tothe residue was added 1 ml of polyphosphoric acid, followed by stirringat 180° C. overnight. After cooling to room temperature, the reactionmixture was neutralized with 1N aqueous solution of sodium hydroxide andsaturated aqueous solution of sodium hydrogen carbonate underice-cooling. The mixture was extracted with ethyl acetate, and theresulting organic layer was washed with brine and dried over anhydrousmagnesium sulfate. The solvent was evaporated, and the residue waspurified by silica gel chromatography (hexane/ethyl acetate system), togive 3 mg of the title compound as white crystals.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.31-7.38(m,4H), 7.45.7.57(m,8H),7.69-7.71(m,1H), 8.29(d,1H), 8.49(d,1H).

ESI-Mass; 399 [M⁺+H]

Example 1853-(2-Chlorophenyl)-5-phenoxymethyl-1-phenyl-1,2-dihydropyridin-2-one

24 mg of3-(2-Chlorophenyl)-5-hydroxymethyl-1-phenyl-1,2-dihydropyridin-2-one wasdissolved in 10 ml of tetrahydrofuran. 9.4 mg of phenol, 33 mg oftriphenylphosphine polymer (3 mmol/g resin) and 17 mg of1,1′-azobis(N,N-dimethylformamide) were added thereto, followed bystirring at 60° C. overnight. Further, 50 mg of triphenylphosphinepolymer (3 mmol/g resin) and 30 mg of 1,1′-azobis(N,N-dimethylformamide)were added, followed by stirring at 60° C. overnight. After cooling toroom temperature, ethyl acetate was added thereto and thetriphenylphosphine polymer was removed by filtration through Celite. Thefiltrate was washed with water and 1N aqueous solution of sodiumhydroxide. The organic layer was washed with brine and dried overanhydrous magnesium sulfate. The solvent was evaporated, and the residuewas purified by silica gel chromatography (hexane/ethyl acetate system),to give 12 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 4.87(s, 2H), 6.97(dd, 2H), 7.01(dd,1H),7.26-7.34(m,4H), 7.40-7.51(m,7H), 7.54-7.56(m,1H), 7.60(d,1H).

ESI-Mass; 388 [M⁺+H]

Example 1863-(2-Cyanophenyl)-5-(1-methyl-1,2,3,6-tetrahydropyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

99 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one wasdissolved in 10 ml of acetonitrile. 2 ml of methyl benzenesulfonate wasadded thereto, followed by stirring at 100° C. for 2 nights. Aftercooling to room temperature, the solvent was evaporated. The residue wasdissolved in 10 ml of methanol, followed by cooled to 0° C. understirring. Sodium borohydride was added 5 times at intervals of 5 hours,1 g for each time, followed by further stirring at 0° C. overnight. Thenthe solvent was evaporated and a saturated aqueous solution of ammoniumchloride was added to the residue, followed by extracting with ethylacetate. The organic layer was washed with brine and dried overanhydrous magnesium sulfate. The solvent was evaporated, and the residuewas purified by silica gel chromatography (hexane/ethyl acetate system),to give 107 mg of3-bromo-5-(1-methyl-1,2,3,6-tetrahydropyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one.The product was dissolved in 10 ml of dimethylformamide. 81 mg of2-(2-cyanophenyl)-1,3,2-dioxaborinate, 142 mg of cesium carbonate and 7mg of tetrakistriphenylphosphine palladium were added thereto, followedby stirring at 140° C. for 2 hours. After cooling to room temperature,water was added thereto, followed by extracting with ethyl acetate. Theorganic layer was washed with brine and dried over anhydrous magnesiumsulfate. The solvent was evaporated, and the residue was purified bysilica gel chromatography (hexane/ethyl acetate system), to give 41 mgof the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.26(s,3H), 2.30-2.50(m,1H),2.90-2.98(m,1H), 3.15(dd,1H), 3.31-3.40(m,1H), 3.85(t,1H),5.72-5.78(m,1H), 5.79-5.85(m,1H), 7.40(d,1H), 7.40-7.57(m,5H),7.60(td,1H), 7.64-7.70(m,1H), 7.72-7.73(m,1H), 7.74-7.75(m,1H),7.76(d,1H).

Example 1873-(2-Pyridylethenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

23 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one wasdissolved in 20 ml of acetonitrile. To the mixture were added 0.2 mg ofpalladium acetate, 4.3 mg of tri-o-tolylphosphine and 0.04 ml oftriethylamine, followed by stirring at 110° C. in nitrogen atmosphereovernight. To the mixture was added 9.2 mg of 2-vinylpyridine, followedby stirring at 110° C. in nitrogen atmosphere for 5 hours. After coolingto room temperature, the reaction mixture was poured into water,followed by extracting with ethyl acetate. The organic layer was washedwith brine and dried over anhydrous magnesium sulfate. The solvent wasevaporated, and the residue was purified by silica gel chromatography(hexane/ethyl acetate system), to give 2 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.12-7.16(m,1H), 7.18-7.23(m,1H),7.36(d,1H), 7.44-7.51(m,3H), 7.51-7.55(m,2H), 7.57-7.60(m,1H),7.64(dt,1H), 7.70-7.79(m,1H), 7.78-7.82(m,1H), 8.03-8.07(m,1H),8.24(d,1H), 8.28(d,1H), 8.57-8.63(m,2H).

ESI-Mass; 352 [M⁺+H]

Example 1883-(4-Chlorophenylthio)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

25 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one wasdissolved in 20 ml of dimethylformamide. To the mixture were added 3 mgof sodium hydroxide and 2 mg of copper iodide, followed by stirring at150° C. in nitrogen atmosphere overnight. After cooling to roomtemperature, the reaction mixture was poured into water. An aqueousammonia was added thereto, followed by extracting with ethyl acetate.The organic layer was washed with brine and dried over anhydrousmagnesium sulfate. The solvent was evaporated, and the residue waspurified by silica gel chromatography (hexane/ethyl acetate system), togive 8 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.17(ddd,1H), 7.30(d,1H),7.39-7.56(m,9H), 7.61(d,1H), 7.67(td,1H), 8.08(d,1H), 8.52-8.54(m,1H).

ESI-Mass; 391 [M⁺+H]

Example 1893-(2-Chlorophenyl)-5-cyclohexyl-1-phenyl-1,2-dihydropyridin-2-one

30 mg of 5-bromo-3-(2-chlorophenyl)-1-phenyl-1,2-dihydropyridin-2-onesynthesized from 5-bromo-1-phenyl-3-iodo-1,2-dihydropyridin-2-one and2-chlorophenyl boronic acid in accordance with the method of ReferentialExample 3 was dissolved in 20 ml of tetrahydrofuran, followed by adding1 mg of [1,3-bis(diphenylphosphino)propane]nickel (II) chloride. Understirring in nitrogen atmosphere, 0.1 ml of cyclohexyl magnesium chloride(2.0M ether solution) was added dropwise thereinto. After stirring atroom temperature in nitrogen atmosphere overnight, the mixture washeated under reflux for 1 hour. After cooling to room temperature, asaturated aqueous solution of ammonium chloride was added thereto,followed by extracting with ethyl acetate. The organic layer was washedwith brine and dried over anhydrous magnesium sulfate. The solvent wasevaporated, and the residue was purified by silica gel chromatography(chloroform/methanol system), to give 6 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.15-1.47(m,5H), 1.53-1.93(m,5H),2.35(m,1H), 6.99-7.34(m,3H), 7.36-7.60(m,8H).

ESI-Mass; 364 [M⁺+H]

Example 1903-(1H-Benzimidazol-2-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

25 mg of carboxylate obtained by de-protecting the ester group of3-methoxycarbonyl-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one in aconvention manner was dissolved in 20 ml of dichloromethane. Underice-cooling, a solution of 16 mg of oxalyl chloride in dichloromethanewas added dropwise thereinto and a catalytic amount of dimethylformamidewas added thereto, followed by stirring at room temperature in nitrogenatmosphere for 1 hour. The reaction solution was evaporated, and to theresidue was added dichloromethane. The solution was added dropwise intoa solution of 17 mg of o-phenylenediamine in dichloromethane underice-cooling. After heating to room temperature, the mixture was stirredin nitrogen atmosphere overnight. Dichloromethane was evaporated,followed by adding methanol and heating under reflux for 5 hours. Aftercooling to room temperature, the reaction mixture was poured into anice-cooled saturated aqueous solution of sodium hydrogen carbonate,followed by extracting with ethyl acetate. The organic layer was washedwith brine and dried over anhydrous magnesium sulfate. The solvent wasevaporated, and the residue was refined by silica gel chromatography(hexane/ethyl acetate system), to give 1.3 mg of the title compound aswhite crystals.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.10-7.94(m,13H), 8.57(d,1H),8.60(m,1H), 9.43(d,1H).

ESI-Mass; 365 [M⁺+H]

Example 1913-(2-Pyridon-1-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

40 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one and 23mg of 2-hydroxypyridine were dissolved in 10 ml of dimethylformamide. 34mg of potassium carbonate and 3 mg of copper iodide were added thereto,followed by stirring at 140° C. overnight. After cooling the reactionmixture to room temperature, an aqueous ammonia was added thereto,followed by extracting with ethyl acetate. The organic layer was washedwith brine and dried over magnesium sulfate. The solvent was evaporated,and the residue was purified by silica gel chromatography (NH silica)(chloroform/methanol system), to give 10 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.24(td,1H), 6.69(dd,1H), 7.22(dd,1H),7.37-7.42(m,2H), 7.45-7.57(m,6H), 7.73(td,1H), 8.33(d,1H), 8.36(d,1H),8.58-8.60(m,1H).

Example 192 3-Cyclohexyl-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

34 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one wasdissolved in 10 ml of tetrahydrofuran, followed by adding 1 mg of[1,3-bis(diphenylphosphino)propane]nickel (II) chloride. Under stirringin nitrogen atmosphere, 0.1 ml of cyclohexyl magnesium chloride (2.0Mether solution) was added dropwise thereinto. The mixture was stirred atroom temperature in nitrogen atmosphere for 1 hour, followed by heatingunder reflux for 72 hours. After cooling to room temperature, water wasadded thereto, followed by extracting with ethyl acetate. The organiclayer was washed with brine, and then dried over anhydrous magnesiumsulfate. The solvent was evaporated, and the residue was purified bysilica gel chromatography (chloroform/methanol system), to give 5 mg ofthe title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.22-1.52(m,5H), 1.73-1.80(m,1H)1.81-1.89(m,2H), 1.97-2.04(m,2H), 2.90-2.99(m,1H), 7.18(ddd,1H),7.53-7.55(m,6H), 7.71(td,1H), 7.78(dd,1H), 8.04(d,1H), 8.59(ddd,1H).

Example 1933-[2-(5-Methyl-1,2,4-oxadiazol-3-yl)phenyl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

53 mg of3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one wasdissolved in 10 ml of ethanol containing 20% of water. 19 mg ofhydroxylamine hydrochloride and 17 mg of sodium acetate were addedthereto, followed by heating under reflux for 24 hours. Further, 19 mgof hydroxylamine hydrochloride and 17 mg of sodium acetate were addedthereto, followed by heating under reflux for 36 hours. After cooling toroom temperature, the mixture was evaporated, and the resulting crystalswere washed with water, dried, and 50 mg of amidoxime compound wascollected by filtration. 20 mg of the product was dissolved in 4 ml oftoluene. 16 mg of acetic anhydride was added thereto, followed byheating under reflux for 96 hours. After cooling to room temperature,the mixture was neutralized with potassium carbonate under ice-cooling.After extracting with ethyl acetate, the extract was successively washedwith water and brine, and dried over anhydrous magnesium sulfate. Thesolvent was evaporated, and the residue was purified by silica gelchromatography (hexane/ethyl acetate system), to give 4 mg of the titlecompound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.56(s, 3H), 7.18(ddd, 1H), 7.38-7.59(m,8H), 7.72(ddd, 1H), 7.71(ddd, 1H), 8.08(ddd, 1H), 8.11(d, 1H), 8.27(d,1H), 8.58(ddd, 1H).

ESI-Mass; 410 [M⁺+H]

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 1.

Example 1943-(2-Cyanophenyl)-5-(1-methylpyrazol-4-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 4.01(s, 3H), 7.46-7.56(m, 8H),7.62-7.68(m, 3H), 7.78-7.81(m, 2H).

Example 1953-(2-Cyanophenyl)-5-(6-methylpyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.56(s, 3H), 7.07(d, 1H), 7.40-7.66(m,9H), 7.76-7.80(m, 2H), 8.28(d, 1H), 8.30(d, 1H).

Example 1963-(2-Cyanophenyl)-5-(5-methylpyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.36(s, 3H), 7.42-7.56(m, 8H), 7.63(dt,1H), 7.76-7.80(m, 2H), 8.26(d, 1H), 8.28(d, 1H), 8.41-8.42(m, 1H).

Example 1973-(2-Cyanophenyl)-5-(4-methylpyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.36(s, 1H), 7.43-7.57(m, 8H), 7.63(dt,1H), 7.77-7.80(m, 2H), 8.27(d, 1H), 8.28(d, 1H), 8.41-8.42(m, 1H).

Example 1983-(2-Cyanophenyl)-5-(3-hydroxypyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.20(dd, 1H), 7.31(dd, 1H), 7.51-7.60(m,6H), 7.68(dd, 1H), 7.75(dt, 1H), 7.83(dd, 1H), 8.11(dd, 1H), 8.51(d,1H), 8.55(d, 1H).

Example 1993-(2-Cyanophenyl)-1-phenyl-5-(2-pyrazyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.46-7.57(m, 6H), 7.66(dt, 1H),7.75-7.81(m, 2H), 8.33(d, 1H), 8.35(d, 1H), 8.50(d, 1H), 8.55(dd, 1H),8.93(d, 1H).

Example 2003-(2-Cyanophenyl)-5-(2-methoxypyridin-5-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.69(s,3H), 6.67(d,1H), 7.18(d,1H),7.44-7.66(m,8H), 7.78-7.81(m,2H), 8.27(d,1H), 8.34(d,1H).

Example 2013-(2-Cyanophenyl)-1-phenyl-5-(2-thiazoyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.31(d,1H), 7.45-7.56(m,6H),7.65(dt,1H), 7.72(dd,1H), 7.77-7.80(m,2H), 8.18(d,1H), 8.25(d,1H).

Example 2023-(2-Cyanophenyl)-1-phenyl-5-(4-pyrimidinyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.46-7.59(m,7H), 7.66(dt,1H),7.76-7.81(m,2H), 8.31(d,1H), 8.56(d,1H), 8.74(d,1H), 9.16(d,1H).

Example 2033-(2-Cyanophenyl)-1-phenyl-5-(5-pyrimidinyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.47-7.58(m,6H), 7.66(dt,1H),7.75(d,1H), 7.78-7.81(m,2H), 7.92(d,1H), 8.92(s,2H), 9.22(s,1H).

Example 2043-(2-Cyanophenyl)-1-phenyl-5-(3-pyridazyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.46-7.56(m,7H), 7.66(dt,1H),7.77-7.83(m,3H), 8.32(d,1H), 8.54(d,1H), 9.15(dd,1H).

Example 2053-(2-Cyanophenyl)-1-phenyl-5-(4-pyridazyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.48-7.61(m, 7H), 7.67(dt, 1H),7.79-7.83(m,2H), 7.92(d,1H), 8.00(d,1H), 9.23(dd,1H), 9.40(dd, 1H).

Example 2063-(2-Cyanophenyl)-5-(2-methoxypyridin-6-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.96(s,3H), 6.67(dd,1H), 7.18(dd, 1H),7.44-7.66(m, 8H), 7.77-7.81(m, 2H), 8.27(d, 1H), 8.33(d, 1H).

Example 2073-(2-Cyanophenyl)-1-phenyl-5-(thiazol-4-yl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.46-7.57(m, 6H), 7.66(ddd, 1H),7.72-7.81(m, 3H), 7.87(d, 1H), 7.97(s, 1H), 8.76(s, 1H).

Example 2083-(2-Cyanophenyl)-5-(3-oxo-1-cyclohexen-1-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.12-2.19(m,2H), 2.46-2.50(m,2H),2.65-2.69(m,2H), 6.36(s,1H), 7.45-7.57(m,6H), 7.62-7.70(m,2H),7.76-7.79(m,2H), 7.88(d,1H).

Example 2093-(2-Cyanophenyl)-5-(5,6-dihydro-1,4-dioxin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 4.12-4.14(m,2H), 4.21-4.23(m,2H),7.42-7.78(m,12H).

Example 2103-(2-Cyanophenyl)-5-(1-naphthyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.41-7.67(m,9H), 7.55-7.83(m,2H),7.88-7.94(m,2H), 8.02(ddd,1H), 8.11(d,1H), 8.70(d,1H), 8.83(d,1H).

ESI-Mass; 400 [M⁺+H]

Example 2113-(2-Cyanophenyl)-5-(2-naphthyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.44-7.58(m,4H), 7.61-7.70(m,3H),7.78-7.82(m,2H), 7.83-7.90(m,2H), 7.92(d,1H), 7.95-7.96(m,1H),8.00(ddd,1H), 8.12(d,1H), 8.72(dd,1H), 8.83(d,1H).

ESI-Mass; 400 [M⁺+H]

Example 2123-(2-Cyanophenyl)-5-(8-quinolinyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.43-7.50(m,3H), 7.60-7.69(m,2H),7.77(m,1H), 7.81-7.87(m,2H), 8.03-8.10(m,2H), 8.18(d,1H), 8.23(dd,1H),8.68-8.72(m,2H), 8.87(d,1H), 8.98(dd,1H).

ESI-Mass; 401 [M⁺+H]

Example 2133-(2-Cyanophenyl)-5-(3-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, DMSO-d₆); δ(ppm) 7.45-7.51(m, 1H), 7.59(ddd, 1H),7.64(dd, 1H), 7.75-7.82(m, 2H), 7.94(d, 1H), 8.10(ddd, 1H),8.15-8.20(m,1H), 8.28(d,1H), 8.39-8.41(m,1H), 8.53-8.56(m,1H), 8.69(dd,1H), 8.84(d, 1H), 8.98-8.90(m, 1H).

ESI-Mass; 351 [M⁺+H]

Example 2145-[(1-Benzenesulfonyl)indol-2-yl]-3-(2-cyanophenyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.70(d, 1H), 7.23-7.43(m, 4H),7.45-7.56(m, 5H), 7.65(d, 1H), 7.68(td, 2H), 7.78(td, 2H), 7.83(d,1H),8.02(ddd,1H), 8.30(dd,1H), 8.72(dd,1H), 8.79(d,1H).

ESI-Mass; 529 [M⁺+H]

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 2.

Example 2151-(4-Aminophenyl)-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.86(brs, 1H), 6.76(td, 2H),7.20(ddd,1H), 7.28(td,2H), 7.44(dt,1H), 7.60(td,1H), 7.64(dd, 1H),7.71-7.80(m,3H), 8.28(d,1H), 8.29(d,1H), 8.60(ddd,1H).

Example 2165-(3-Aminopyridin-2-yl)-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 4.05(br s,2H), 7.07-7.08(m,2H),7.42-7.47(m,2H), 7.51-7.53(m,4H), 7.62(ddd,1H), 7.75-7.78(m,1H),7.79-7.82(m,1H), 7.99(dd,1H), 8.06(dd,1H), 8.15(dd,1H).

Example 2175-(5-Aminopyridin-2-yl)-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.77(brs,2H), 7.04(dd,1H),7.39-7.52(m,7H), 7.60-7.64(m,1H), 7.76-7.80(m,2H), 8.08(dd,1H),8.13(d,1H), 8.22(d,1H).

Example 2181-(3-Aminophenyl)-3-(2-cyanophenyl)-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.85(brs, 2H), 6.76(ddd, 1H), 6.84(t,1H), 6.86(ddd, 1H), 7.14(t, 1H), 7.27-7.31(m, 1H), 7.45(dt, 1H),7.63(dt, 1H), 7.71-7.78(m, 2H), 8.69-8.71(m, 3H), 8.75(d, 1H).

Example 2193-(2-Aminophenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, DMSO-d₆); δ(ppm) 7.23-7.37(m,3H), 7.40-7.47(m,1H),7.47-7.56(m,2H), 7.56-7.66(m,5H), 7.88(ddd,1H), 8.08(d,1H), 8.46(d,1H),8.58(d,1H), 8.59-8.64(m,1H).

Example 2203-(3-Aminophenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.70(br s,2H), 6.68-6.72(m,1H),7.13-7.26(m,3H), 7.42-7.56(m,5H), 7.56-7.60(m,1H), 7.64-7.76(m, 2H),8.22(s, 2H), 8.58-8.61(m, 1H).

Example 2213-(4-Aminophenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.77(br s,2H), 6.70-6.76(m,2H),7.17-7.21(m,1H), 7.42-7.60(m,6H), 7.64-7.75(m,3H), 8.15(s,2H),8.58-8.61(m,1H).

Example 2223-(2-Cyanophenyl)-5-(2-pyridyl)-1-(2-aminotoluen-4-yl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.21(s, 3H), 3.76(s, 2H), 6.78-6.83(m,2H), 7.17(d, 1H), 7.20(ddd, 1H), 7.44(td, 1H), 7.58(d,1H), 7.63(td,1H),7.73(td,1H), 7.78(td,2H), 8.29(s,2H), 8.59(ddd,1H).

ESI-Mass; 379 [M⁺+H]

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 3.

Example 2233-Benzenesulfonylamino-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.22(ddd, 1H), 7.31-7.33(m, 2H),7.44-7.60(m, 7H), 7.76(dt, 1H), 7.92-7.95(m, 2H), 7.97(d, 1H), 8.21(d,1H), 8.56-8.58(m, 1H).

Example 2243-(2-Cyanophenyl)-5-benzenesulfonylamino-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.26-7.27(m,1H), 7.30-7.33(m,2H),7.41-7.65(m,10H), 7.70-7.73(m,1H), 7.83-7.86(m,2H).

Example 2253-(2-Cyanophenyl)-5-[(3-methanesulfonylamino)pyridin-2-yl]-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.40(s,3H), 7.43-7.48(m,4H)7.50-7.54(m,4H), 7.64-7.66(m,2H), 7.74(dd,1H), 7.95(d,1H), 8.20(d,1H),8.77(dd,1H).

Example 2263-[2-(Methylsulfonylamino)phenyl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.96(s,3H), 7.25(ddd,1H),7.30-7.35(m,1H), 7.43-7.63(m,9H), 7.76(ddd,1H), 8.30(brs,1H),8.33(d,1H), 8.39(d,1H), 8.60-8.64(m,1H).

Example 2273-[4-(Methanesulfonylamino)phenyl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.01(s, 3H), 6.57(br s, 1H),7.20-7.28(m,3H), 7.45-7.61(m,6H), 7.77(ddd,1H), 7.79-7.85(m,2H),8.22(d,1H), 8.24(d,1H), 8.60-8.64(m,1H).

Example 2283-[3-(Methanesulfonylamino)phenyl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.92(s,3H), 6.98(br s,1H),7.20-7.32(m,2H), 7.36-7.61(m,8H), 7.69-7.78(m,2H), 8.22(d,1H),8.26(d,1H), 8.59-8.63(m,1H).

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 11.

Example 2295-[(6-Acetylamino)pyridin-2-yl]-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.22(s,3H), 7.33(dd,1H),7.44-7.80(m,10H), 7.85(d,1H), 8.08-8.12(m,1H), 8.24(d,1H), 8.28(d, 1H).

Example 2303-[2-(Acetylamino)phenyl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, DMSO-d₆); δ(ppm) 1.96(s,3H), 7.19-7.26(m,1H),7.30(ddd,1H), 7.34-7.40(m,1H), 7.40-7.46(m,1H), 7.48-7.56(m,1H),7.56-7.64(m,4H), 7.72(d,1H), 7.83(ddd,1H), 8.01(d,1H), 8.32(d,1H),8.50(d,1H), 8.57-8.61(m,1H), 9.16(br s,1H).

Example 2313-[2-(Diacetylamino)phenyl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.28(s, 6H), 7.18(ddd, 1H), 7.23-7.27(m,1H), 7.42-7.60(m, 9H), 7.71(ddd, 1H), 7.95(d, 1H), 8.35(d, 1H),8.54-8.58(m, 1H).

Example 2323-[3-(Acetylamino)phenyl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.11(s,3H), 7.19-7.23(m,1H),7.34-7.40(m,1H), 7.42-7.56(m,6H), 7.60(d,1H), 7.64-7.77(m,3H),7.83-7.87(m,1H), 8.24(d,1H), 8.26(d,1H), 8.58-8.62(m,1H).

Example 2333-[4-(Acetylamino)phenyl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.15(s, 3H), 7.21(ddd, 1H), 7.34(brs,1H), 7.44-7.57(m, 8H), 7.59(ddd, 1H), 7.74(ddd, 1H), 7.80(d, 1H),8.21(s, 2H), 8.59-8.62(m, 1H).

The following compound was synthesized by the method similar to, or inaccordance with, the method for Example 12.

Example 2343-(4-Dimethylaminophenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.00(s, 6H), 6.75-6.80(m, 2H),7.19(ddd,1H), 7.41-7.54(m,5H), 7.57-7.60(m,1H), 7.73(ddd,1H),7.76-7.81(m, 2H), 8.14-8.17(m, 2H), 8.58-8.61(m, 1H).

The following compound was synthesized by the method similar to, or inaccordance with, the method for Example 15.

Example 2355-[(6-Aminocarbonyl)pyridin-2-yl]-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.46-7.60(m, 6H), 7.64(dt, 1H),7.74(dd,1H), 7.80-7.83(m,1H), 7.91-7.95(m,2H), 8.14-8.17(m,2H),8.52(d,1H).

The following compounds were synthesized by the methods similar to, orin accordance with, the method of Example 16, Route 1.

Example 2363-(2-Cyanophenyl)-5-(2-cyanopyridin-6-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.46-7.57(m, 6H), 7.60(dd, 1H),7.66(dt,1H), 7.79-7.83(m,3H), 7.89(dd,1H), 8.29(d,1H), 8.41(d, 1H).

Example 2373-(3-Hydroxyphenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, DMSO-d₆); δ(ppm) 6.74-6.78(m,1H), 7.15-7.26(m,3H),7.27-7.32(m, 1H), 7.47-7.61(m, 5H), 7.83(ddd, 1H), 8.02(d, 1H),8.41(s,2H), 8.57-8.62(m, 1H), 9.43(brs, 1H).

Example 2383-(4-Hydroxyphenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, DMSO-d₆); δ(ppm) 6.79-6.84(m, 2H), 7.28(ddd, 1H),7.47-7.59(m, 5H), 7.61-7.66(m, 2H), 7.82(ddd, 1H), 8.00(d, 1H), 8.33(d,1H), 8.35(d, 1H), 8.57-8.61(m, 1H), 9.57(br s, 1H).

The following compounds were synthesized by the same methods as inExample 19.

Example 2393-(2-Cyanophenyl)-1-[3-(dimethylaminoethoxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.34(s, 6H), 2.74(t, 2H), 4.10(t, 2H),7.01-7.05(m, 1H), 7.07-7.11(m, 2H), 7.21(ddd, 1H), 7.42(dd, 1H),7.45(ddd, 1H), 7.59-7.66(m, 2H), 7.72-7.81(m, 3H), 8.30(s, 2H),8.58-8.61(m, 1H).

Example 2403-(2-Cyanophenyl)-1-[3-(piperidinoethoxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.39-1.48(m,2H), 1.56-1.64(m,4H),2.46-2.56(m,4H), 2.78(t,2H), 4.14(t,2H), 6.99-7.03(m,1H), 7.06-7.11(m,2H), 7.21(ddd, 1H), 7.41(dd, 1H), 7.45(ddd, 1H), 7.59-7.66(m, 2H),7.72-7.81(m, 3H), 8.30(s, 2H), 8.58-8.61(m, 1H).

Example 2413-(2-Cyanophenyl)-1-[3-(pyrrolidinoethoxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.76-1.86(m,4H), 2.57-2.70(m,4H),2.92(t,2H), 4.16(t,2H), 7.03(ddd,1H), 7.06-7.11(m,2H), 7.21(ddd,1H),7.41(dd,1H), 7.45(ddd,1H), 7.59-7.66(m,2H), 7.72-7.81(m,3H), 8.30(s,2H),8.58-8.61(m,1H).

Example 2423-(2-Cyanophenyl)-1-[3-(diisopropylaminoethoxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.03(d,12H), 2.83(t,2H),3.04(heptet,2H), 3.92(t,2H), 6.97-7.01(m,1H), 7.04(dd,1H), 7.07(ddd,1H),7.21(ddd,1H), 7.41(dd,1H), 7.45(ddd,1H), 7.59-7.66(m,2H),7.72-7.82(m,3H), 8.29-8.32(m,2H), 8.58-8.61(m,1H).

Example 2433-(2-Cyanophenyl)-1-[3-(dimethylaminopropyloxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.96(tt,2H), 2.24(s,6H), 2.44(t,2H),4.05(t,2H), 7.00(ddd,1H), 7.05-7.09(m,2H), 7.21(ddd,1H), 7.41(dd,1H),7.45(ddd,1H), 7.59-7.66(m,2H), 7.72-7.81(m,3H), 8.30(s,2H),8.58-8.61(m,1H).

Example 2443-(2-Cyanophenyl)-1-[3-(piperidinopropyloxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.37-1.50(m,2H), 1.53-1.64(m,4H),1.97(tt,2H), 2.30-2.45(m,4H), 2.47(t,2H), 4.04(t,2H), 6.97-7.02(m,1H),7.04-7.09(m,2H), 7.21(ddd,1H), 7.41(dd,1H), 7.45(ddd,1H),7.59-7.66(m,2H), 7.70-7.82(m,3H), 8.31(s,2H), 8.58-8.62(m,1H).

Example 2453-(2-Cyanophenyl)-1-[3-(morpholinoethoxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.48-2.65(m,4H), 2.81(t,2H),3.68-3.80(m,4H), 4.15(t,2H), 6.99-7.04(m,1H), 7.06-7.13(m,2H),7.22(ddd,1H), 7.42(dd,1H), 7.46(ddd,1H), 7.61(dd,1H), 7.64(ddd,1H),7.74(ddd,1H), 7.78(dd,2H), 8.28-8.33(m,2H), 8.58-8.62(m,1H).

Example 2463-(2-Cyanophenyl)-1-[3-(diethylaminoethoxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.07(t,6H), 2.64(q,4H), 2.89(t,2H),4.08(t,2H), 7.01(ddd,1H), 7.05-7.10(m,2H), 7.21(ddd,1H), 7.41(dd,1H),7.45(ddd,1H), 7.59-7.66(m,2H), 7.72-7.81(m,3H), 8.31(s,2H),8.58-8.61(m,1H).

Example 2473-[3-(Dimethylaminoethoxy)phenyl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.34(s,6H), 2.74(t,2H), 4.13(t,2H),6.92-6.98(m,1H), 7.19-7.24(m,1H), 7.33(dd,1H), 7.37-7.42(m,1H),7.44-7.56(m,6H), 7.57-7.62(m,1H), 7.75(ddd,1H), 8.25(s,2H),8.59-8.63(m,1H).

Example 2483-[4-(Dimethylaminoethoxy)phenyl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.35(s,6H), 2.76(t,2H), 4.12(t,2H),6.95-7.00(m,2H), 7.20(ddd,1H), 7.43-7.54(m,5H), 7.59(ddd,1H),7.73(ddd,1H), 7.76-7.81(m,2H), 8.17-8.20(m,2H), 8.59-8.62(m,1H).

Example 2493-(2-Cyanophenyl)-1-[3-(4-piperidinobutyl-1-oxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.38-1.46(m,2H), 1.54-1.61(m,4H),1.62-1.71(m,2H), 1.75-1.83(m,2H), 2.30-2.43(m,6H), 4.01(t,2H),6.97-7.01(m,1H), 7.03-7.08(m,2H), 7.21(ddd,1H), 7.40(dd,1H),7.45(ddd,1H), 7.59-7.66(m,2H), 7.72-7.82(m,3H), 8.30(s,2H),8.58-8.61(m,1H).

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 29.

Example 2503-(2-Cyanophenyl)-1-[3-(pyrrolidinomethyl)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.74-1.84(m,4H), 2.48-2.58(m,4H),3.69(s,2H), 7.14-7.25(m,2H), 7.38-7.51(m,4H), 7.61(d,1H), 7.63(ddd,1H),7.72-7.82(m,3H), 8.30(d,1H), 8.32(d,1H), 8.58-8.62(m,1H).

Example 2511-{3-[(4-Acetylpiperazino)methyl]phenyl}-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.07(s,3H), 2.45(dd,4H), 3.45(dd,2H),3.58(s,2H), 3.63(dd,2H), 7.22(ddd,1H), 7.40-7.54(m,5H), 7.60-7.67(m,2H),7.73-7.80(m,3H), 8.29(d,1H), 8.33(d,1H), 8.58-8.62(m,1H).

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 32.

Example 2523-(2-Cyanophenyl)-1-(4-nitrophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.24-7.30(m,1H), 7.47-7.52(m,1H),7.61-7.82(m,7H), 8.31(dd,1H), 8.42(d,1H), 8.60-8.63(m,1H).

Example 2531-Phenyl-3-(2-pyrazyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.21-7.25(m,1H), 7.49-7.59(m,5H)7.72-7.79(m,2H), 8.46(d,1H), 8.54(d,1H), 8.61(ddd,1H), 8.65(dd,1H),9.14(d,1H), 9.87(d,1H).

Example 2541-Phenyl-3-(2-pyrimidinyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.20(ddd,1H), 7.25(t,1H),7.44-7.54(m,4H), 7.66(d,1H), 7.75(dt,1H), 8.45(d,1H), 8.58-8.60(m,1H),8.82(d,1H), 8.88(s,1H), 8.89(s,1H).

Example 2551-Phenyl-5-(2-pyridyl)-3-(2-thiazoyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.22-7.26(m,1H), 7.48-7.57(m,6H),7.78-7.80(m,1H), 8.00(dd,1H), 8.52(dd,1H), 8.59-8.61(m,1H), 9.29(d,1H).

Example 2561-Phenyl-3-(4-pyrimidinyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.22-7.26(m,1H), 7.48-7.59(m,5H),7.77-7.82(m,2H), 8.53(d,1H), 8.60-8.62(m,1H), 8.73-8.77(m,2H),9.27(dd,1H), 9.40(d,1H).

Example 2571-Phenyl-3-(5-pyrimidinyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.24-7.27(m,1H), 7.48-7.61(m,7H),7.77(dt,1H), 8.28(d,1H), 8.37(d,1H), 8.63(ddd,1H), 9.21(d,1H),9.22(s,1H).

Example 2581-Phenyl-3-(3-pyridazyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.22-7.25(m,1H), 7.48-7.58(m,6H),8.55(d,1H), 8.60(m,1H), 8.78(dd,1H), 9.14(dd,1H), 9.34(d,1H).

Example 2591-Phenyl-3-(4-pyridazyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.24-7.28(m,1H), 7.47-7.62(m,6H),7.78(dt,1H), 8.16(dd,1H), 8.33(d,1H), 8.53(d,1H), 8.63-8.65(m,1H),9.23(dd,1H), 9.62(dd,1H).

Example 2603-(2-Methoxypyridin-6-yl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 4.07(s,3H), 6.73(dd,1H),7.46-7.56(m,5H), 7.62-7.70(m,2H), 7.78(ddd,1H), 8.35(dd,1H), 8.39(d,1H),8.66(ddd,1H), 9.21(d,1H).

Example 2613-(2-Cyanophenyl)-1-(3-pyridyl)-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.18(t,1H), 7.46-7.52(m,2H),7.65(dt,1H), 7.71(dd,1H), 7.74-7.80(m,1H), 7.99(ddd,1H),8.72-8.75(m,5H), 8.82(dd,1H).

Example 2623-(2-Fluoropyridin-3-yl)-1-phenyl-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.16(t,1H), 7.24-7.27(m,2H),7.48-7.57(m,5H), 8.19-8.23(m,2H), 8.69-8.76(m,3H).

Example 2633-(2-Fluoropyridin-3-yl)-1-(3-pyridyl)-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.19(t,1H), 7.26-7.30(m,1H),7.47-7.52(m,1H), 7.94(ddd,1H), 8.17(ddd,1H), 8.70-8.80(m,7H).

Example 2643-(2-Cyanopyridin-3-yl)-1-phenyl-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.17(t,1H), 7.47-7.56(m,6H),8.14(dd,1H), 8.70(dd,1H), 8.72(d,1H), 8.80(d,1H), 8.85(d,1H).

Example 2653-(2-Cyanopyridin-3-yl)-1-(3-pyridyl)-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.20(t, 1H), 7.52(ddd, 1H), 7.58(dd,1H), 7.97(ddd, 1H), 8.11(dd, 1H), 8.71-8.76(m, 4H), 8.78(d, 1H),8.81(dd, 1H), 8.66(d, 1H).

Example 2663-(2-Cyanophenyl)-1-(3-nitrophenyl)-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.20(t, 1H), 7.49(ddd, 1H), 7.65-7.80(m,5H), 7.98(ddd, 1H), 8.36(ddd, 1H), 8.46(t, 1H), 8.73-8.77(m, 4H).

Example 2671-Phenyl-5-(2-pyridyl)-3-(thiazol-4-yl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.24-7.28(m,1H), 7.48-7.58(m,5H),7.64(td,1H), 7.79(dt,1H), 8.23(d,1H), 8.58(d,1H), 8.64-8.66(m,2H),8.85(d,1H).

Example 2683-(3-Oxo-1-cyclohexen-1-yl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.09-2.16(m,2H), 2.48-2.51(m,2H),2.87-2.91(m, 2H), 6.53(t, 1H), 7.22(ddd, 1H), 7.43-7.57(m, 6H), 7.75(dt,1H), 8.17(d, 1H), 8.25(d, 1H), 8.60(ddd, 1H).

Example 2693-(5,6-Dihydro-1,4-dioxin-2-yl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 4.18-4.20(m,2H), 4.30-4.32(m,2H),7.19(ddd,1H), 7.41-7.54(m,5H), 7.63(td,1H), 7.73(dt,1H), 8.02(s,1H),8.28(d,1H), 8.58(ddd,1H).

Example 2703-(2-Nitrophenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.22(ddd,1H), 7.40-7.61(m,8H),7.68(ddd,1H), 7.74(ddd,1H), 8.06(dd,1H), 8.22-8.25(m,2H),8.60-8.63(m,1H).

Example 2713-(4-Biphenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.20-7.25(m,1H), 7.33-7.40(m,1H),7.42-7.57(m,6H), 7.60-7.79(m,7H), 7.90-7.95(m,2H), 8.25(d,1H),8.30(d,1H), 8.60-8.64(m,1H).

Example 2723-(2-Acetylphenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.59(s,3H), 7.16-7.21(m,1H),7.40-7.60(m,8H), 7.63-7.67(m,1H), 7.68-7.75(m,1H), 8.16(d,1H),8.22(d,1H), 8.57-8.61(m,1H).

Example 2733-(3-Nitrophenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.24(ddd, 1H), 7.46-7.64(m, 7H),7.76(ddd, 1H), 8.20-8.26(m, 2H), 8.27(d, 1H), 8.37(d, 1H), 8.61-8.65(m,1H), 8.69(dd, 1H).

Example 2741-Phenyl-3-(4-pyridyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.24(ddd, 1H), 7.46-7.62(m, 6H),7.73-7.81(m, 3H), 8.28(d, 1H), 8.39(d, 1H), 8.61-8.64(m, 1H), 8.66(dd,2H).

Example 2753-(4-Nitrophenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.22-7.26(m,1H), 7.47-7.58(m,5H),7.60(ddd,1H), 7.76(ddd,1H), 8.01-8.06(m,2H), 8.26-8.31(m,3H),8.38(d,1H), 8.61-8.65(m,1H).

Example 2761-[3-(Benzyloxy)phenyl]-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 5.10(s,2H), 7.05-7.14(m,2H),7.17(dd,1H), 7.21(ddd,1H), 7.30-7.48(m, 7H), 7.60(ddd, 1H), 7.64(ddd,1H), 7.71-7.81(m,3H), 8.29-8.32(m,2H), 8.58-8.61(m,1H).

Example 2771-(3-Acetylphenyl)-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.66(s, 3H), 7.24(ddd, 1H), 7.48(ddd,1H), 7.61-7.69(m, 3H), 7.74-7.81(m, 4H), 8.07(ddd, 1H) 8.11(ddd, 1H),8.32(d, 1H), 8.34(d, 1H), 8.59-8.62(m, 1H).

Example 2783-[4-(tert-Butylaminosulfonyl)phenyl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.26(s, 9H), 4.46(s, 1H), 7.24(ddd,1H),7.46-7.58(m,5H), 7.58-7.61(m,1H), 7.76(ddd,1H), 7.90-7.99(m, 4H),8.26(d, 1H), 8.33(d, 1H), 8.61-8.64(m, 1H).

Example 2793-(1-Naphthyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.21(dd, 1H), 7.42-7.50(m, 3H),7.51-7.61(m,3H), 7.71(td,1H), 7.81-7.85(m,1H), 7.87-7.90(m,2H),7.96-7.99(m,1H), 8.20(d,1H), 8.37(d,1H), 8.60(d,1H), 8.67(d,1H),8.84(d,1H).

ESI-Mass; 376 [M⁺+H]

Example 2803-(1-Naphthyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.19(ddd, 1H), 7.38-7.59(m, 9H),7.71(td, 2H), 7.84-7.89(m, 3H), 8.18(d, 1H), 8.39(d, 1H), 8.59(ddd, 1H).

ESI-Mass; 375 [M⁺+H]

Example 2813-(8-Quinolinyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.18-7.23(m,1H), 7.38-7.56(m,3H),7.84-7.58(m,3H), 7.86-8.01(m,3H), 8.19-8.23(m,1H), 8.30-8.36(m,2H),8.56-8.62(m,1H), 8.66-8.70(m,1H), 8.91-8.97(m,1H).

ESI-Mass; 377 [M⁺+H]

Example 2823-(8-Quinolinyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.18(dd, 1H), 7.39-7.54(m, 4H),7.55-7.65(m, 3H), 7.66-7.73(m, 2H), 7.85(dd, 1H), 7.98(dd, 1H), 8.2(dd,1H), 8.34(d, 1H), 8.36(d, 1H), 8.58(d, 1H), 8.94(dd, 1H).

ESI-Mass; 376 [M⁺+H]

Example 2833-(2-Naphthyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.23-7.28(m,1H), 7.48-7.53(m,3H),7.64(dt, 1H), 7.78(td, 1H), 7.85-7.91(m, 4H), 7.97(ddd, 1H), 8.25(d,1H),8.35(s,1H), 8.38(d,1H), 8.64(ddd,1H), 8.72(d,1H), 8.81(d,1H).

ESI-Mass; 376 [M⁺+H]

Example 2843-(2-Naphthyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.21(dd,1H), 7.44-7.50(m,4H),7.53-7.56(m,3H), 7.62(dd,1H), 7.72-7.77(m,1H), 7.83-7.91(m,2H),7.92(td,2H), 8.25(d,1H), 8.37(d,1H), 8.39(brs,1H), 8.61-8.64(m,1H).

Example 2853-(2-Pyrrolidinopyridin-5-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.00-2.04(m,4H), 3.50(t,4H),7.74-7.78(m,9H), 8.03(d,1H), 8.06(d,1H), 8.21(d,1H), 8.57-8.60(m,2H).

ESI-Mass; 396 [M⁺+H]

Example 2863-(2-Formylthiophen-3-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.21-7.29(m,2H), 7.46-7.57(m,6H),7.73(d,1H), 7.75(td,1H), 8.22(d,1H), 8.31(d,1H), 8.60-8.62(m,1H),10.00(s,1H).

ESI-Mass; 359 [M⁺+H]

Example 2873-(2-Chloropyridin-5-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.24(ddd,1H), 7.37(d,1H),7.44-7.51(m,3H), 7.53-7.60(m,2H), 7.64-7.70(m,1H), 7.76(td,1H),8.24(d,1H), 8.26(t,1H), 8.31(d,1H), 8.62(ddd,1H), 8.75(d,1H).

ESI-Mass; 360 [M⁺+H]

Example 2883-(2-Fluoropyridin-5-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.99(dd, 1H), 7.24(dd, 1H), 7.47-7.57(m,5H), 7.59(dd, 1H), 7.76(tdd, 1H), 8.25(dd, 1H), 8.30(dd, 1H), 8.37(td,1H), 8.57-8.58(m, 1H), 8.63(dt, 1H).

Example 2893-(2-Ethylthiopyridin-5-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.39(t, 3H), 3.20(q, 2H), 7.20-7.24(m,2H), 7.44-7.59(m, 6H), 7.75(td, 1H), 8.08(dd, 1H), 8.23(d, 1H), 8.26(d,1H), 8.61(ddd, 1H), 8.78(d, 1H).

ESI-Mass; 386 [M⁺+H]

Example 2903-(2-Cyanophenyl)-5-(2-pyridyl)-1-(2-naphthyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.22(ddd, 1H), 7.47(td, 1H),7.53-7.60(m,2H), 7.62-7.67(m,3H), 7.76(td,1H), 7.81(td,2H), 7.88-7.94(m,2H), 7.98(d, 1H), 7.99(s, 1H), 8.34(d, 1H), 8.43(d,1H), 8.60(ddd, 1H).

ESI-Mass; 400 [M⁺+H]

Example 2913-(2-Cyanophenyl)-5-(2-pyridyl)-1-(1-naphthyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.21(ddd,1H), 7.45(td,1H),7.54-7.65(m,6H), 7.65-7.83(m,4H), 7.93-8.02(m,2H), 8.30(d,1H),8.46(d,1H), 8.57(ddd,1H).

ESI-Mass; 400 [M⁺+H]

Example 2923-(2-Cyanophenyl)-5-(2-pyridyl)-1-(8-quinolinyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.18(ddd,1H), 7.43(td,1H), 7.48(dd,1H),7.61(td,1H), 7.63(d,1H), 7.69(dd,1H), 7.72(td,1H), 7.78(dd,1H),7.86(dd,1H), 7.92(dd,1H), 7.98(dd,1H), 8.26(dd,1H), 8.36(d,1H),8.43(d,1H), 8.55-8.57(m,1H), 8.95(dd,1H).

Example 2933-[(1-Benzenesulfonyl)indol-2-yl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.95(d, 1H), 7.21(ddd, 1H),7.22(ddd,1H), 7.26-7.33(m,3H), 7.42(dt,1H), 7.44-7.49(m,2H),7.50-7.56(m,4H), 7.60(dt,1H), 7.71-7.77(m,3H), 8.07(dd,1H), 8.20(d, 1H),8.34(d, 1H), 8.60(ddd, 1H).

Example 2943-(2-Cyanopyridin-3-yl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.20-7.28(m, 1H), 7.51(dd, 1H), 7.58(dd,1H), 7.64(d, 1H), 7.79(td, 1H), 7.94-7.97(m, 1H), 8.18(dd,1H),8.35(d,1H), 8.44(d,1H), 8.60-8.63(m,1H), 8.72(dd, 1H), 8.74(dd, 1H),8.81(d, 1H).

ESI-Mass; 352 [M⁺+H]

Example 2953-(2-Cyanophenyl)-5-(2-pyridyl)-1-(pyrrol-3-yl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.46-6.50(m, 1H), 6.79(dd, 1H), 7.21(dd,1H), 7.29-7.32(m, 1H), 7.45(t, 1H), 7.60-7.66(m, 2H), 7.72-7.80(m,3H),8.23(d,1H), 8.47(d,1H), 8.61(d,1H), 8.72(brs, 1H).

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 162.

Example 2963-(2-Cyanophenyl)-5-(3-nitropyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.43-7.54(m,7H), 7.62-7.67(m,2H),7.73-7.76(m, 2H), 8.03(d, 1H), 8.24(dd, 1H), 8.82(dd, 1H).

Example 2973-(2-Cyanophenyl)-5-[2-(2,6-dimethylpyrrol-1-yl)pyridin-6-yl]-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.17(s,6H), 5.91(s,2H), 7.12(dd,1H),7.45-7.56(m, 6H), 7.61(dd, 1H), 7.65(dd, 1H), 7.78-7.80(m, 1H), 7.88(t,1H), 8.35(d, 1H), 8.40(d, 1H).

Example 2985-(2-Aminopyridin-6-yl)-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 4.44(brs, 2H), 6.43(dd, 1H), 6.96(d,1H), 7.42-7.54(m, 7H), 7.63(dt, 1H), 7.76-7.78(m, 1H), 8.24(d, 1H),8.26(d, 1H).

Example 2993-(2-Cyanophenyl)-5-(5-nitropyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.47-7.59(m, 6H), 7.67(dt, 1H),7.75-7.82(m,3H), 8.35(d,1H), 8.52(dd,1H), 8.55(d,1H), 9.39(dd, 1H).

Example 3005-(2-Bromopyridin-6-yl)-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.39(dd, 1H), 7.45-7.67(m, 9H),7.78-7.80(m, 2H), 8.23(d, 1H), 8.34(d, 1H).

Example 3013-(2-Cyanophenyl)-1-phenyl-5-(5-trifluoromethylpyridin-2-yl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.46-7.58(m,6H), 7.63-7.68(m,1H),7.72(d,1H), 7.78-7.81(m,1H), 7.97(ddd,1H), 8.33(d,1H), 8.44(d, 1H),8.83-8.84(m, 1H).

Example 3023-(2-Cyanophenyl)-5-(2-morpholinopyridin-6-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.55(t,2H), 3.83(t,2H), 6.57(d,1H),6.97(d,1H), 7.43-7.66(m,8H), 7.77-7.80(m,2H), 8.18(d,1H), 8.31(d,1H).

Example 3033-(2-Cyanophenyl)-5-(2-methoxycarbonylpyridin-6-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.99(s, 3H), 7.44-7.57(m, 6H),7.65(dt,1H), 7.78-7.81(m,3H), 7.91(t,1H), 8.04(dd,1H), 8.30(d, 1H),8.37(d, 1H).

The following compound was synthesized by the method similar to, or inaccordance with, the method for Example 164.

Example 3045-[4-(tert-Butylaminosulfonyl)phenyl]-3-(2-cyanophenyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.25(s, 9H), 4.72(br s, 1H),7.47-7.54(m,2H), 7.60-7.71(m,4H), 7.73-7.83(m,2H), 7.93-8.02(m,4H),8.73(dd,1H), 8.79(d,1H).

The following compound was synthesized by the method similar to, or inaccordance with, the method for Example 167.

Example 3053-(2-Cyanophenyl)-4-methyl-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.12(s,3H), 7.28(ddd,1H),7.38-7.52(m,8H), 7.59(s,1H), 7.66(ddd,1H), 7.75-7.80(m,2H),8.66-8.70(m,1H).

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 168.

Example 3061-Phenyl-3-[N—(N′-phenylthioureylenyl)]-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.19-7.24(m,1H), 7.26-7.36(m,3H),7.37-7.54(m, 7H), 7.70(d, 1H), 7.78(ddd, 1H), 7.92(br s, 1H), 8.09(d,1H), 8.55-8.59(m, 1H), 9.33(br s, 1H), 10.03(d, 1H).

Example 3073-(2-Cyanophenyl)-1-phenyl-5-[N—(N′-phenylureylenyl)]-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, DMSO-d₆); δ(ppm) 6.95(dd, 1H), 7.25(dd, 1H),7.41-7.61(m,8H), 7.65(d,1H), 7.71(d,1H), 7.77(dd,1H), 7.92(d, 1H),8.03(d, 1H), 8.56-8.66(m, 1H), 9.02-9.10(m, 1H).

Example 3083-{4-[N—(N′-butylureylenyl)phenyl]}-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, DMSO-d₆); δ(ppm) 0.90(t,3H), 1.32(tt, 2H), 1.42(tt,2H),3.09(dt,2H), 6.16(br t,1H), 7.29(dd,1H), 7.44(d,2H), 7.47-7.54(m,1H),7.54-7.60(m,4H), 7.69(d,2H), 7.82(ddd,1H), 8.02(d,1H), 8.35(d,1H),8.39(d,1H), 8.53(br s,1H), 8.58-8.61(m,1H).

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 169.

Example 3093-(2-Cyanophenyl)-1-phenyl-5-(2-pyridincarbonyl)amino-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.42-7.54(m,7H), 7.63(ddd,1H),7.74-7.79(m,3H), 7.92(ddd,1H), 8.20(d,1H), 8.58(d,1H), 8.59-8.62(m,1H),9.80(br s,1H).

Example 3101-Phenyl-3-[2-(1-pyrrolidino)acetylamino]-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.78-1.86(m,4H), 2.66-2.74(m,4H),3.36(s,2H), 7.20(ddd,1H), 7.44-7.56(m,5H), 7.66(d,1H), 7.75(ddd,1H),8.07(d,1H), 8.54-8.58(m,1H), 9.12(d,1H), 10.15(br s,1H).

Example 3111-Phenyl-3-{3-[1-(4-phenylpiperadino)]propionylamino}-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.66(t,2H), 2.69-2.76(m,4H), 2.80(t,2H),3.30-3.36(m,4H), 6.81-6.86(m,1H), 6.90-6.97(m,2H), 7.18(ddd,1H),7.22-7.29(m,2H), 7.40-7.53(m,5H), 7.62-7.67(m,1H), 7.73(ddd,1H),8.03(d,1H), 8.53-8.57(m,1H), 9.11(d,1H), 10.56(br s,1H).

Example 3123-(3-pyrrolidinopropionyl)amino-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.80-1.88(m,4H), 2.58-2.67(m,6H),2.86(t,2H), 7.17(ddd,1H), 7.42-7.54(m,5H), 7.65(d,1H), 7.73(ddd,1H),8.03(d,1H), 8.53-8.57(m,1H), 9.11(d,1H), 10.91(br s,1H).

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 170.

Example 3135-Benzylamino-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 4.15(s,2H), 6.70(d,1H), 7.30-7.36(m,1H),7.36-7.43(m,8H), 7.43-7.49(m,3H), 7.59(ddd,1H), 7.72-7.77(m,2H).

Example 3143-Dibenzylamino-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 4.52(s,4H), 7.12(ddd,1H),7.16-7.33(m,10H), 7.37-7.54(m,7H), 7.63(ddd,1H), 7.80(d,1H),8.50-8.54(m,1H).

Example 3153-(2-Cyanophenyl)-1-(3-hydroxyphenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

52 mg of1-[3-(benzyloxy)phenyl]-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-oneand 20 mg of 5% palladium-carbon were added to 3 ml of methanol,followed by stirring at room temperature in hydrogen atmosphereovernight. After the resulting insoluble matters were filtered off, thefiltrate was evaporated. The residue was purified by silica gelchromatography (ethyl acetate/hexane system), to give 26 mg the titlecompound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.76(dd,1H), 6.87-6.92(m,1H),6.93(dd,1H), 7.22-7.30(m,2H), 7.44(ddd,1H), 7.60-7.67(m,2H),7.73-7.80(m,3H), 8.25(d,1H), 8.32(d,1H), 8.33(br s,1H), 8.59-8.63(m,1H).

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 171.

Example 3161-Benzyloxymethyl-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 4.76(s,2H), 5.63(s,2H), 7.22(ddd,1H),7.26-7.42(m,5H), 7.47(ddd,1H), 7.57(d,1H), 7.64-7.80(m,4H), 8.23(d,1H),8.34(d,1H), 8.60-8.64(m,1H).

Example 3173-(2-Cyanophenyl)-1-cyclopentylmethyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.32-1.42(m,2H), 1.55-1.64(m,2H),1.65-1.75(m,2H), 1.76-1.86(m,2H), 2.53(ddd,1H), 4.10(d,2H),7.21(ddd,1H), 7.45(ddd,1H), 7.58(d,1H), 7.64(ddd,1H), 7.71-7.79(m,3H),8.16(d,1H), 8.28(d,1H), 8.59-8.63(m,1H).

Example 3181-[1-(tert-butoxycarbonyl)piperidin-4-yl]methyl-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.22-1.35(m,2H), 1.45(s,9H),1.68-1.78(m,2H), 2.14-2.27(m,1H), 2.61-2.76(m,2H), 3.90-4.25(m,4H),7.22(ddd,1H), 7.46(ddd,1H), 7.58(ddd,1H), 7.65(ddd,1H), 7.73(ddd,2H),7.78(dd,1H), 8.17(d,1H), 8.21(d,1H), 8.59-8.63(m,1H).

Example 3191-[1-(Benzyloxycarbonyl)piperidin-4-yl]methyl-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.25-1.38(m,2H), 1.68-1.81(m,2H),2.17-2.30(m,1H), 2.70-2.86(m,2H), 3.92-4.08(m,2H), 4.15-4.32(m,2H),5.12(s,2H), 7.22(ddd,1H), 7.28-7.38(m,5H), 7.46(ddd,1H), 7.57(d,1H),7.65(ddd,1H), 7.69-7.79(m,3H), 8.17(d,1H), 8.20(d,1H), 8.59-8.62(m,1H).

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 174.

Example 3203-(Pyrrol-1-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.33(t,2H), 7.22(ddd,1H), 7.36(t,2H),7.45-7.57(m,6H), 7.74(td,1H), 8.10(d,1H), 8.12(d,1H), 8.61(ddd,1H).

ESI-Mass; 314 [M⁺+H]

Example 3213-(2-Cyanophenylamino)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.06(ddd,1H), 7.21(ddd,1H),7.41-7.65(m,9H), 7.71(td,1H), 7.76(d,1H), 7.88(d,1H), 8.60(ddd,1H).

ESI-Mass; 365 [M⁺+H]

Example 3223-(2-Pyridylamino)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.80-6.86(m, 2H), 7.20(dd, 1H),7.44-7.58(m,6H), 7.70(d,1H), 7.77(td,1H), 7.87(d,1H), 7.96(s, 1H),8.37(d, 1H), 8.59(d, 1H), 9.29(d, 1H).

ESI-Mass; 341 [M⁺+H]

Example 3233-(1-Isoguinolylamino)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.15-7.24(m,3H), 7.46-7.59(m,5H),7.66(t,1H), 7.77(d,2H), 7.80(td,1H), 7.97(d,1H), 8.10(d,1H), 8.25(d,1H),8.61(d,1H), 9.11(s,1H), 9.60(d,1H).

ESI-Mass; 391 [M⁺+H]

Example 3243-(1-Indazolyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.52(dt,1H), 7.06(ddd,1H), 7.22(ddd,1H),7.31(td,1H), 7.36(ddd,1H), 7.43-7.57(m,7H), 7.75(dt,1H), 8.03(s,1H),8.09(d,1H), 8.50(dd,1H).

ESI-Mass; 365 [M⁺+H]

Example 3253-(9-Carbazolyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.22-7.29(m,4H), 7.35-7.63(m,9H),7.52-7.57(m,1H), 8.12(dd,2H), 8.43(dd,1H), 8.46(dd,1H), 8.61(ddd,1H).

Example 3263-(Indol-1-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.68(d, 1H), 7.17(td, 1H), 7.20-7.26(m,2H), 7.47-7.55(m, 7H), 7.62(d, 1H), 7.66(d, 1H), 7.74(td, 1H), 8.27(d,1H), 8.34(d, 1H), 8.61(ddd, 1H).

ESI-Mass; 364 [M⁺+H]

Example 3273-(2-Methyl-5-phenylpyrrol-1-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

25 mg of 3-amino-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one wasdissolved in 10 ml of toluene. To the mixture were added 20 mg of1-phenyl-1,4-pentandione and 0.2 mg of p-toluenesulfonate (hydrate),followed by heating under reflux for 1 hour. After cooling to roomtemperature, the reaction mixture was poured into a saturated aqueoussolution of sodium hydrogen carbonate, followed by extracting with ethylacetate. The organic layer was washed with brine and dried overanhydrous magnesium sulfate. The solvent was evaporated, and the residuewas purified by silica gel chromatography (hexane/ethyl acetate system),to give 12 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.26(s,3H), 6.10(d,1H), 6.34(d,1H),7.21(tt, 1H), 7.17(ddd, 1H), 7.21-7.27(m, 2H), 7.28-7.32(m, 3H),7.39-7.54(m, 5H), 7.66(td, 1H), 7.83(d, 1H), 8.31(d, 1H), 8.53(ddd, 1H).

The following compounds were synthesized by the method similar to, or inaccordance with, the method for Example 327.

Example 3283-(2,5-Dimethylpyrrol-1-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.16(s,6H), 5.92(s,2H), 7.22(ddd, 1H),7.56-7.43(m, 6H), 7.75(td, 1H), 8.07(d, 1H), 8.37(d, 1H), 8.60(ddd, 1H).

Example 3293-(2-Cyanophenyl)-1-(piperidin-4-yl)methyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

The titled compound (382 mg) was obtained by catalytically hydrogenating590 mg of1-[1-(benzyloxycarbonyl)piperidin-4-yl]methyl-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-oneusing in a conventional manner using 10% palladium-carbon.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.22-1.34(m,2H), 1.62-1.77(m,2H),2.08-2.20(m,1H), 2.55-2.63(m,2H), 3.05-3.13(m,2H), 4.00(d,2H),7.21(ddd,1H), 7.45(ddd,1H), 7.58(ddd,1H), 7.64(ddd,1H), 7.70-7.79(m,3H),8.17(d,1H), 8.21(d,1H), 8.59-8.63(m,1H).

The following compound was synthesized by the method similar to, or inaccordance with, the method for Example 329.

Example 3303-(2-Cyanophenyl)-1-[3-(4-piperidyloxy)]phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.60-1.73(m,2H), 1.98-2.07(m,2H),2.69-2.77(m,2H), 3.08-3.17(m,2H), 4.39-4.46(m,1H), 6.98-7.02(m,1H),7.04-7.09(m,2H), 7.21(ddd,1H), 7.38-7.48(m,2H), 7.58-7.67(m,2H),7.72-7.81(m,3H), 8.29-8.32(m,2H), 8.58-8.61(m,1H).

Example 3311-(1-Benzoylpiperidin-4-yl)methyl-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

30 mg of3-(2-cyanophenyl)-1-(piperidin-4-yl)methyl-5-(2-pyridyl)-1,2-dihydropyridin-2-onewas dissolved in 2 ml of chloroform. Under ice-cooling, 0.04 ml oftriethylamine and 19 mg of benzoyl chloride were added thereto, followedby stirring at room temperature for 2 hours. The reaction solution wasdiluted with chloroform, and washed with a saturated aqueous solution ofsodium hydrogencarbonate and brine. The organic layer was dried overmagnesium sulfate, and then evaporated and the residue was purified bysilica gel chromatography (ethyl acetate/hexane), to give 25 mg of thetitle compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.22-1.52(m,2H), 1.65-1.78(m,1H),1.80-1.98(m,1H), 2.28-2.41(m,1H), 2.70-2.86(m,1H), 2.88-3.06(m,1H),3.70-3.88(m,1H), 3.90-4.23(m,2H), 4.65-4.87(m,1H), 7.22(dd,1H),7.36-7.42(m,5H), 7.46(dd,1H), 7.55-7.60(m,1H), 7.62-7.72(m,2H),7.72-7.79(m,2H), 8.16(d,1H), 8.22(d,1H), 8.59-8.63(m,1H).

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 331.

Example 3321-(1-Acetylpiperidin-4-yl)methyl-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.22-1.38(m,2H), 1.75-1.86(m,2H),2.08(s,3H), 2.20-2.35(m,1H), 2.50-2.60(m,1H), 2.98-3.08(m,1H),3.79-3.87(m,1H), 3.95(dd,1H), 4.05-4.15(m,1H), 4.61-4.70(m,1H),7.23(ddd,1H), 7.47(ddd,1H), 7.58(d,1H), 7.63-7.71(m,2H),7.72-7.80(m,2H), 8.17(d,1H), 8.21(d,1H), 8.59-8.63(m,1H).

Example 3331-[3-(N-acetylpiperidin-4-yl-oxy)phenyl]-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.77-2.02(m,4H), 2.12(s,3H),3.37-3.45(m,1H), 3.59-3.72(m,2H), 3.75-3.83(m,1H), 4.57-4.62(m,1H),7.01(ddd,1H), 7.07-7.12(m,2H), 7.22(ddd,1H), 7.43(dd,1H), 7.46(ddd,1H),7.61(ddd,1H), 7.64(ddd,1H), 7.72-7.80(m, 3H), 8.29(d, 1H), 8.31(d, 1H),8.58-8.62(m, 1H).

Example 3341-[3-(N-benzoylpiperidin-4-yl-oxy)phenyl]-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.75-2.13(m,4H), 3.30-3.47(m,1H),3.58-3.72(m,1H), 3.75-3.87(m,1H), 3.88-4.03(m,1H), 4.56-4.68(m,1H),6.99-7.03(m,1H), 7.07-7.13(m,2H), 7.20-7.25(m,1H), 7.38-7.49(m,7H),7.59-7.67(m,2H), 7.72-7.80(m,3H), 8.28(d,1H), 8.31(d,1H),8.58-8.62(m,1H).

Example 3351-[1-(Benzenesulfonyl)piperidin-4-yl]methyl-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

30 mg of3-(2-cyanophenyl)-1-(piperidin-4-yl)methyl-5-(2-pyridyl)-1,2-dihydropyridin-2-onewas dissolved in 2 ml of chloroform. Under ice-cooling, 0.04 ml oftriethylamine and 23 mg of benzenesulfonyl chloride were added thereto,followed by stirring at room temperature for 2 hours. The reactionsolution was diluted with chloroform, and washed with a saturatedaqueous solution of sodium hydrogen carbonate and brine. The organiclayer was dried over magnesium sulfate, and then evaporated and theresidue was purified by silica gel chromatography (ethylacetate/hexane), to give 30 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.41-1.60(m,2H), 1.77-1.85(m,2H),1.95-2.06(m,1H), 2.20-2.31(m,2H), 3.80-3.88(m,2H), 3.98(d,2H),7.22(dd,1H), 7.45(ddd,1H), 7.48-7.68(m,6H), 7.70-7.79(m,4H), 8.15(d,1H),8.17(d,1H), 8.59-8.63(m,1H).

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 335.

Example 3363-(2-Cyanophenyl)-1-[1-(methanesulfonyl)piperidin-4-yl]methyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.43-1.56(m,2H), 1.83-1.92(m,2H),2.17-2.30(m,1H), 2.63-2.72(m,2H), 2.77(s,3H), 3.80-3.88(m,2H),4.03(d,2H), 7.20-7.26(m,1H), 7.44-7.51(m,1H), 7.55-7.61(m,1H),7.63-7.72(m,2H), 7.73-7.82(m,2H), 8.17(d,1H), 8.21(d,1H),8.59-8.64(m,1H).

Example 3371-{3-[1-(Benzenesulfonyl)piperidin-4-yl-oxy]phenyl}-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.90-2.10(m,4H), 3.10-3.23(m,4H),4.38-4.45(m,1H), 6.87-6.92(m,1H), 6.98(dd,1H), 7.05(ddd,1H),7.22(ddd,1H), 7.38(dd,1H), 7.46(ddd,1H), 7.52-7.66(m,5H),7.72-7.80(m,5H), 8.25-8.28(m,2H), 8.57-8.60(m,1H).

Example 3383-(2-Cyanophenyl)-1-{3-[1-(methanesulfonyl)piperidin-4-yl-oxy]phenyl}-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.98-2.10(m, 4H), 2.81(s, 3H),3.30-3.41(m, 4H), 4.56-4.62(m, 1H), 6.98-7.02(m, 1H), 7.08-7.13(m, 2H),7.23(ddd, 1H), 7.44(dd, 1H), 7.47(ddd, 1H), 7.61(ddd, 1H), 7.65(ddd,1H), 7.73-7.80(m, 3H), 8.28(d, 1H), 8.32(d, 1H), 8.59-8.62(m, 1H).

Example 3393-(2-Cyanophenyl)-1-(1-benzylpiperidin-4-yl)methyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

80 mg of3-(2-cyanophenyl)-1-(piperidin-4-yl)methyl-5-(2-pyridyl)-1,2-dihydropyridin-2-onewas dissolved in 2 ml of chloroform. To the mixture were added 73 mg ofbenzaldehyde, 97 mg of triacetoxy sodium borohydride and 41 mg of aceticacid, followed by stirring at room temperature for 4 hours. The reactionsolution was diluted with chloroform, and washed with a saturatedaqueous solution of sodium hydrogen carbonate and brine. The organiclayer was dried over magnesium sulfate. Then the mixture was evaporated,and the residue was purified by NH silica gel chromatography(hexane/ethyl acetate system), to give 80 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.44(ddd,2H), 1.68-1.76(m,2H),1.92-2.06(m,3H), 2.37-2.93(m,2H), 3.48(s,2H), 4.01(d,2H),7.18-7.25(m,2H), 7.27-7.32(m,4H), 7.45(ddd,1H), 7.56(d,1H),7.64(ddd,1H), 7.70-7.78(m,3H), 8.16(d,1H), 8.19(d,1H), 8.58-8.61(m,1H).

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 339.

Example 3403-(2-Cyanophenyl)-1-(1-methylpiperidin-4-yl)methyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.38-1.50(m,2H), 1.65-1.80(m,2H),1.88-2.05(m,3H), 2.25(s,3H), 2.82-2.92(m,2H), 4.01(d,2H),7.19-7.24(m,1H), 7.43-7.49(m,1H), 7.56-7.60(m,1H), 7.62-7.68(m,1H),7.70-7.80(m,3H), 8.17(d,1H), 8.20(d,1H), 8.59-8.63(m,1H).

Example 3411-[3-(N-methylpiperidin-4-yl-oxy)phenyl]-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.80-1.93(m,2H), 1.97-2.08(m,2H),2.23-2.37(m,5H), 2.60-2.73(m,2H), 4.33-4.42(m,1H), 6.97-7.02(m,1H),7.04-7.10(m,2H), 7.19-7.24(m,1H), 7.38-7.49(m,2H), 7.58-7.68(m,2H),7.72-7.82(m,3H), 8.28-8.33(m,2H), 8.58-8.62(m,1H).

Example 3421-[3-(N-benzylpiperidin-4-yl-oxy)phenyl]-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.78-1.88(m,2H), 1.97-2.06(m,2H),2.26-2.35(m, 2H), 2.58-2.76(m, 2H), 4.33-4.41(m, 1H), 6.97-7.01(m,1H),7.04-7.08(m,2H), 7.21(ddd,1H), 7.24-7.28(m, 1H), 7.30-7.34(m, 4H),7.40(dd, 1H), 7.46(ddd, 1H), 7.60(ddd, 1H), 7.64(ddd,1H),7.72-7.80(m,3H), 8.30(s,2H), 8.58-8.61(m, 1H).

Example 3433-(4-Sulfamoylphenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

80 mg of3-[4-(tert-butylaminosulfonyl)phenyl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-onewas dissolved in 3 ml of trifluoroacetic acid, followed by heating underreflux for 1 hour. It was left to cool to room temperature, and then thereaction mixture was diluted with ethyl acetate/tetrahydrofuran, andwashed with a saturated aqueous solution of sodium hydrogen carbonateand brine. The organic layer was dried over magnesium sulfate, and thenevaporated. The resulting crude crystals were washed with ethyl acetate,to give 60 mg of the title compound.

¹H-NMR (400 MHz, DMSO-d₆); δ(ppm) 7.31(ddd, 1H), 7.49-7.61(m, 5H),7.82-7.90(m, 3H), 7.97-8.02(m, 2H), 8.03-8.07(m, 1H), 8.48(d,1H),8.54(d, 1H), 8.59-8.62(m, 1H).

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 181.

Example 3443-Cyclohexylaminocarbonyl-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.12-2.10(m,10H), 3.97-4.04(m,1H),7.23(ddd,1H), 7.43-7.58(m,1H), 7.49-7.59(m,4H), 7.74-7.77(m,1H),7.79(td,1H), 8.55-8.56(m,1H), 8.57(d,1H), 9.18(d,1H), 9.64(d,1H).

ESI-Mass; 374 [M⁺+H]

Example 3453-(2-Cyanophenyl)-5-(1-adamantylaminocarbonyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.77-1.56(m,7H), 1.97-2.15(m,8H),5.63(s, 1H), 7.42-7.54(m, 6H), 7.63(td, 1H), 7.74-7.78(m, 2H), 7.88(d,1H), 8.12(d, 1H).

Example 3463-(1-Adamantylaminocarbonyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.50-1.72(m,12H), 1.99-2.15(m,3H),7.21-7.29(m,1H), 7.43-7.49(m,2H), 7.48-7.60(m,4H), 7.75-7.80(m, 1H),8.47(d, 1H), 8.55(d, 1H), 8.60(ddd, 1H).

Example 3473-{1-[4-(2-Cyanophenyl)piperadino]carbonyl}-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.12-3.31(m,4H), 3.59-3.79(m,4H),6.99-7.06(m,2H), 7.22(dd,1H), 7.27-7.62(m,8H), 7.75(td,1H), 8.29(d,1H),8.37(d,1H), 8.58(ddd,1H).

ESI-Mass; 462 [M⁺+H]

Example 3483-[(2-Phenylhydrazino)carbonyl]-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.53(d,1H), 6.89(t,1H), 6.94(d,2H),7.20-7.30(m,3H), 7.62-7.47(m,5H), 7.71-7.77(m,1H), 7.80(dd,1H),8.56-8.57(m,1H), 8.64(d,1H), 9.16(d,1H), 11.23(d,1H).

ESI-Mass; 383 [M⁺+H]

Example 3493-Phenylaminocarbonyl-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.06-7.17(m,1H), 7.23-7.28(m,1H),7.31-7.37(m, 2H), 7.46-7.62(m, 5H), 7.73-7.83(m, 4H), 8.58(ddd,1H),8.63(d, 1H), 9.29(d, 1H), 11.86(brs, 1H).

Example 350

(350A)

3-(2-Chlorophenyl)-5-(4-chlorobenzenesulfinyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

(350B)

3-(2-Chlorophenyl)-5-(4-chlorobenzenesulfonyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

38 mg of3-(2-chlorophenyl)-5-(4-chlorophenylthio)-1-(3-pyridyl)-1,2-dihydropyridin-2-onewas dissolved in 10 ml of dichloromethane. Under ice-cooling, 15.4 mg ofm-chloroperbenzoic acid was added thereto, followed by stirring at thesame temperature for 1 hour. Further, 10 mg of m-chloroperbenzoic acidwas added thereto, followed by stirring for 2 hours under ice-cooling.Then, the mixture was diluted with 30 ml of ethyl acetate, and washedwith an aqueous solution of 1N sodium hydroxide. The organic layer waswashed with brine, and then dried over anhydrous magnesium sulfate. Thesolvent was evaporated, and the residue was purified by silica gelchromatography (hexane/ethyl acetate system), to give 9 mg of3-(2-chlorophenyl)-5-(4-chlorobenzenesulfinyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-oneand 6 mg of3-(2-chlorophenyl)-5-(4-chlorobenzenesulfonyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-oneas the title compounds.

(350A)

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.27-7.33(m,3H), 7.36(d,1H)7.40-7.44(m,1H), 7.48-7.57(m,3H), 7.63-7.67(m,2H), 7.87-7.92(m,1H),7.97(d,1H), 8.70-8.76(m,2H).

ESI-Mass; 441 [M⁺+H]

(350B)

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.30-7.37(m,2H), 7.44-7.52(m,3H),7.56(t,1H), 7.58(t,1H), 7.34(d,1H), 7.84-7.88(m,1H), 7.89(t,1H),7.92(t,1H), 8.24(d,1H), 8.71(dd,1H), 8.75(dd,1H).

ESI-Mass; 457 [M⁺+H]

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 182.

Example 3513-(2-Cyanophenyl)-5-(5-methyl-1H-benzimidazol-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.45(s, 3H), 7.05(d, 1H), 7.34-7.43(m,7H), 7.57(td, 2H), 7.62(ddd, 1H), 7.68(ddd, 1H), 8.18(d, 1H), 8.27(d,1H).

ESI-Mass; 403 [M⁺+H]

Example 3523-(2-Cyanophenyl)-5-(4-methyl-1H-benzimidazol-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.50(brs, 1.5H), 2.63(brs, 1.5H),7.02(d, 1H), 7.14(t, 1H), 7.30-7.40(m, 7H), 7.52-7.58(m, 2H), 7.65(d,1H), 8.18-8.23(m, 1H), 8.24(d, 1H).

ESI-Mass; 403 [M⁺+H]

Example 3533-(2-Cyanophenyl)-5-(5,6-dichloro-1H-benzimidazol-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.39-7.49(m,6H), 7.52-7.54(m,1H),7.60-7.66(m,2H), 7.70-7.72(m,1H), 7.72-7.74(m,1H), 8.21(d,1H),8.37(d,1H).

ESI-Mass; 457 [M⁺+H]

Example 3543-(5,6-Dichloro-1H-benzimidazol-2-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.27(ddd, 1H), 7.48-7.63(m, 6H),7.82(td,1H), 7.83-7.89(m,2H), 8.59(d,1H), 8.60(dt,1H), 9.38(d, 1H),12.15(s, 1H).

ESI-Mass; 433 [M⁺+H]

Example 3553-(6-Chloro-1H-benzimidazol-2-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.22-7.28(m,2H), 7.50-7.63(m,6H),7.78-7.88(m,3H), 8.58(dd,1H), 8.61(ddd,1H), 9.40(d,1H).

ESI-Mass; 399 [M⁺+H]

Example 3563-[1-(Pyridin-4-yl)benzimidazol-2-yl]-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.10-7.13(m,2H), 7.22-7.28(m,2H),7.31-7.46(m, 8H), 7.69(dt, 1H), 7.77(td, 1H), 7.91(dt, 1H), 8.43(d, 1H),8.59(ddd, 1H), 8.73-8.75(m, 2H).

ESI-Mass; 442 [M⁺+H]

Example 3573-[1-(1-Benzylpiperidin-4-yl)benzimidazol-2-yl]-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.01-2.20(m,4H), 2.56-2.66(m,2H),3.02-3.07(m, 2H), 3.58(s, 2H), 4.09-4.18(m, 1H), 7.21(ddd, 1H),7.24-7.30(m, 3H), 7.31-7.36(m, 2H), 7.45-7.50(m, 4H), 7.52-7.60(m, 3H),7.64(d, 1H), 7.74(td, 1H), 7.77-7.84(m, 2H), 8.48(d, 1H), 8.49(d, 1H),8.58(ddd, 1H).

ESI-Mass; 538 [M⁺+H]

Example 3583-(2-Cyanophenyl)-5-(5,6-dihydro-4H-imidazo[4,5,1-i,j]quinolin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.30(qu,2H), 3.02(t,2H), 4.47(t,2H),7.04(dd,1H), 7.20(dd,1H), 7.45-7.57(m,7H), 7.65(td,1H), 7.79(dd,1H),7.81(dd,1H), 8.10(d,1H), 8.22(d,1H).

ESI-Mass; 429 [M⁺+H]

Example 3593-(5,6-Dihydro-4H-imidazo[4,5,1-i,j]quinolin-2-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.20(qu,2H), 2.98(t,2H), 4.35(t,2H),7.03(d, 1H), 7.18-7.23(m, 2H), 7.44-7.58(m, 5H), 7.62(d,1H), 7.70(d,1H),7.75(dt,1H), 8.52(d,1H), 8.57(ddd,1H) 8.70(d,1H).

ESI-Mass; 405 [M⁺+H]

Example 3603-(1-Phenylbenzimidazol-2-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.05-7.21(m,3H), 7.25-7.45(m,6H),7.47-7.65(m,7H), 8.10(d,1H), 8.54-8.59(m,1H), 8.85-8.95(m,1H),9.22(d,1H).

ESI-Mass; 441 [M⁺+H]

Example 3613-(2-Chlorophenyl)-5-(6-chloro-1H-benzimidazol-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.92(td,1H), 6.97-7.07(m,4H),7.11-7.14(m,2H), 7.18-7.24(m,3H), 7.25-7.29(m,2H), 7.94(d,1H),8.24(d,1H).

ESI-Mass; 432 [M⁺+H]

Example 3623-(2-Cyanophenyl)-5-(1H-imidazo[4,5-c]pyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.04-7.09(m,1H), 7.28-7.31(m,1H),7.44-7.60(m,5H), 7.66-7.70(m,2H), 7.74-7.78(m,1H), 7.80(d,1H),7.93-7.96(m,1H), 8.01(d,1H), 8.40(d,1H), 8.51(d,1H).

ESI-Mass; 390 [M⁺+H]

Example 3633-(6-Methyl-1H-benzimidazol-2-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.50(s, 3H), 7.08-7.15(m, 1H),7.23-7.26(m, 1H), 7.45-7.69(m, 7H), 7.81(td, 1H), 7.88(d, 1H), 8.56(d,1H), 8.59(ddd, 1H), 9.40(d, 1H), 11.95-12.07(m, 1H).

ESI-Mass; 379 [M⁺+H]

Example 3643-(5-Methyl-1H-benzimidazol-2-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.49(s, 3H), 7.12(t, 1H), 7.24-7.27(m,1H), 7.31-7.72(m, 7H), 7.80(td, 1H), 7.87(d, 1H), 8.56(d, 1H), 8.59(ddd,1H), 9.40(d, 1H), 11.94-12.07(m, 1H).

ESI-Mass; 379 [M⁺+H]

Example 3653-(2-Cyanophenyl)-5-[1-(1-benzylpiperidin-4-yl)benzimidazol-2-yl]-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.92(dd,2H), 2.36(t,2H), 2.75(ddd,2H),3.05(d,2H), 3.62(s,2H), 4.58(tt,1H), 7.26-7.41(m,7H), 7.44-7.51(m,2H),7.52-7.56(m,4H), 7.65(td,1H), 7.70(dd,1H), 7.72(d,1H), 7.73-7.81(m,3H),8.01(d,1H).

ESI-Mass; 562 [M⁺+H]

Example 3663-(2-Cyanophenyl)-5-(5-methoxy-1H-benzimidazol-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.83(s, 3H), 6.85(dd, 1H),7.24-7.47(m,8H), 7.50(d,2H), 7.60(dt,1H), 8.15(s,1H), 8.16(s, 1H).

ESI-Mass; 419 [M⁺+H]

Example 3673-(1H-Imidazo[4,5-c]pyridin-2-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.19-7.28(m,1H), 7.48-7.63(m,4H),7.69-7.90(m, 2H), 8.08(d, 1H), 8.12(d, 1H), 8.16-8.22(m, 1H), 8.34(d,1H), 8.59(d, 1H), 8.58-8.62(m, 1H), 9.44(d, 1H), 12.20(brs, 1H).

ESI-Mass; 366 [M⁺+H]

Example 3683-(2-Cyanophenyl)-5-[1-(pyridin-4-yl)benzimidazol-2-yl]-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.29-7.34(m,4H), 7.35-7.51(m,8H),7.59(td,1H), 7.69(d,1H), 7.73(dd,1H), 7.82(d,1H), 7.84(dt,1H),8.91(dd,2H).

ESI-Mass; 466 [M⁺+H]

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 183.

Example 3693-(2-Chlorophenyl)-5-(5-trifluoromethylbenzothiazol-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.32-7.37(m,2H), 7.47-7.58(m,7H),7.61(ddd,1H), 7.99(d,1H), 8.14(d,1H), 8.21-8.23(m,1H), 8.39(d, 1H).

ESI-Mass; 483 [M⁺+H]

Example 3703-(5-Trifluoromethylbenzothiazol-2-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.26-7.30(m,1H), 7.51-7.64(m,6H),7.81-7.87(m, 2H), 8.08(d, 1H), 8.39(s, 1H), 8.63(d, 1H), 8.64(t,1H),9.50(d,1H).

ESI-Mass; 450 [M⁺+H]

Example 3713-(2-Benzothiazolyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.26-7.30(m, 1H), 7.41(t, 1H),7.50-7.60(m, 6H), 7.84(t, 1H), 7.88-7.94(m, 1H), 7.98(d, 1H), 8.12(d,1H), 8.60-8.63(m, 2H), 9.48-9.52(m, 1H).

ESI-Mass; 382 [M⁺+H]

Example 3725-(2-Benzothiazolyl)-3-[2-(2-benzothiazolyl)phenyl]-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.09-7.14(m,2H), 7.25-7.33(m,4H),7.37(td,1H), 7.42(td,1H), 7.46-7.52(m,4H), 7.80(ddt,2H), 7.90(ddt,2H),7.95(d,1H), 8.12(d,1H), 8.30(d,1H).

ESI-Mass; 514 [M⁺+H]

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 184.

Example 3735-(2-Benzoxazolyl)-3-[2-(2-benzoxazolyl)phenyl]-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.22-7.42(m,7H), 7.44-7.73(m,9H),8.26(d,1H), 8.34(d,1H), 8.48(d,1H).

ESI-Mass; 482 [M⁺+H]

Example 3743-(2-Benzoxazolyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.22-7.28(m,1H), 7.29-7.32(m,2H),7.42-7.46(m,2H), 7.48-7.50(m,3H), 7.54-7.58(m,1H), 7.70-7.80(m,3H),8.55-8.60(m,2H), 9.03(d,1H).

ESI-Mass; 366 [M⁺+H]

Example 3753-(2-Chlorophenyl)-5-(5-chlorobenzoxazol-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.27-7.35(m,3H), 7.41-7.51(m,4H),7.52-7.57(m, 4H), 7.67(d, 1H), 8.25(d, 1H), 8.49(d, 1H).

ESI-Mass; 433 [M⁺+H]

Example 3763-(5-Chlorobenzoxazol-2-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.26(ddd, 1H), 7.33(dd, 1H),7.47-7.58(m,6H), 7.72(dt,1H), 7.79(d,1H), 7.79(td,1H), 8.55(d, 1H),8.62(ddd, 1H), 9.12(d, 1H).

ESI-Mass; 340 [M⁺+H]

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 315.

Example 3773-[1-(Piperidin-4-yl)benzimidazol-2-yl]-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.01-2.15(m,2H), 2.42-2.52(m,2H),2.66-2.84(m, 2H), 3.20-3.30(m, 2H), 4.21-4.40(m, 1H), 7.19-7.83(m, 12H),8.49(d, 1H), 8.52(d, 1H), 8.56-8.59(m, 1H).

ESI-Mass; 448 [M⁺+H]

Example 378

(378A)

3-(2-Cyanophenyl)-5-[1-(piperidin-4-yl)benzimidazol-2-yl]-1-phenyl-1,2-dihydropyridin-2-one

(378B)

3-(2-Cyanophenyl)-5-[1-(1-methylpiperidin-4-yl)benzimidazol-2-yl]-1-phenyl-1,2-dihydropyridin-2-one

(378A)

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.90-2.02(m, 2H), 2.65(ddd, 2H), 3.01(t,2H), 3.28(d, 2H), 4.69(tt, 1H), 7.27-7.29(m, 2H), 7.47-7.55(m, 6H),7.67(td, 1H), 7.71(d, 1H), 7.67-7.83(m, 4H), 8.05(d, 1H).

ESI-Mass; 472 [M⁺+H]

(378B)

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.90-2.00(m,2H), 2.35-2.40(m,2H),2.41(s, 3H), 2.73-2.87(m, 2H), 3.00-3.10(m,2H), 4.51-4.62(m,1H),7.26-7.30(m, 2H), 7.44-7.54(m, 6H), 7.65(td, 1H), 7.70-7.83(m, 5H),8.03(d, 1H).

ESI-Mass; 486 [M⁺+H]

Example 379

(379A)

3-(2-Cyanophenyl)-5-(2-pyridyl)-1-(piperidin-3-yl)-1,2-dihydropyridin-2-one

(379B)

3-(2-Cyanophenyl)-5-(2-pyridyl)-1-(N-benzylpiperidin-3-yl)-1,2-dihydropyridin-2-one

(379A)

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.90-2.05(m,2H), 2.13-2.22(m,1H),2.35-2.44(m, 1H), 2.70(td, 1H), 3.05-3.12(m, 1H), 3.37(d, 1H),3.60-3.72(m,1H), 4.97-5.05(m,1H), 7.21(ddd,1H), 7.45(td,1H), 7.57(d,1H),7.64(td,1H), 7.68-7.78(m,3H), 8.13(d,1H), 8.48(d, 1H), 8.62(ddd, 1H).

ESI-Mass; 357 [M⁺+H]

(379B)

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.65-1.75(m,2H), 1.92-2.05(m,2H),2.45-2.60(m, 2H), 2.70-2.80(m, 1H), 2.97(dd, 1H), 3.55(s, 2H),5.15-5.20(m, 1H), 7.22(ddd, 1H), 7.27-7.32(m, 1H), 7.40-7.49(m,4H),7.52-7.5(m,2H), 7.61-7.77(m,5H), 8.15(d,1H), 8.65(ddd, 1H).

ESI-Mass; 447 [M⁺+H]

Example 3803-(2-Cyanophenyl)-5-(N-methylpiperidin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.24-1.39(m,2H), 1.73-1.85(m,2H),2.04-2.14(m,3H), 2.16(s,3H), 2.63(dd,1H), 3.00(d,1H), 7.37-7.56(m,5H),7.59(td,1H), 7.64-7.70(m,2H), 7.72-7.74(m,1H), 7.74-7.76(m,2H).

ESI-Mass; 370 [M⁺+H]

The following compound was synthesized by the method similar to themethod for Example 7.

Example 3813-(2-Cyanophenyl)-5-(2-pyridyl)-1-(2-nitrotoluen-4-yl)-1,2-dihydropyridin-2-one

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 2.69(s,3H), 7.23-7.28(m,1H),7.48(td,1H), 7.56-7.51(m,1H), 7.62(d,1H), 7.66(t,1H), 7.74-7.81(m,4H),8.21(d,1H), 8.30(d,1H), 8.32(d,1H), 8.61(d,1H).

Example 382

(382A)

3-(4-Chlorobenzenesulfinyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

(382B)

3-(4-Chlorobenzenesulfonyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

6 mg of3-(4-chlorophenylthio)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-onewas dissolved in 3 ml of dichloromethane. Under ice-cooling, 3 mg ofm-chloroperbenzoic acid was added thereto, followed by stirring at thesame temperature for 30 minutes. After stirring at room temperature for5 hours, the mixture was diluted with 10 ml of ethyl acetate, and washedwith a 1N aqueous solution of sodium hydroxide. The organic layer waswashed with brine, and then dried over anhydrous magnesium sulfate. Thesolvent was evaporated, and the residue was purified by silica gelchromatography (hexane/ethyl acetate system), to give 1.2 mg of3-(4-chlorobenzenesulfinyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-oneand 1.5 mg of3-(4-chlorobenzenesulfonyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-oneas the title compounds.

(382A)

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.23-7.29(m,2H), 7.37-7.54(m,6H),7.72(dt,1H), 7.79(td,1H), 7.87(t,1H), 7.89(t,1H), 8.44(d,1H),8.57-8.60(m,1H), 8.69(d,1H).

ESI-Mass; 407 [M⁺+H]

(382B)

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.22-7.30(m,2H), 7.37-7.40(m,2H),7.42-7.52(m,4H), 7.67(dt,1H), 7.80(td,1H), 8.09(t,1H), 8.11(t,1H),8.58(d,1H), 8.60(ddd,1H), 9.06(d,1H).

ESI-Mass; 423 [M⁺+H]

The following compounds were synthesized by the methods similar to, orin accordance with, the method for Example 382.

Example 383

(383A)

3-(2-Ethylsulfinylpyridin-5-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

(383B)

3-(2-Ethylsulfonylpyridin-5-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

(383A)

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.24(t,3H), 2.96(dt,1H), 3.21(dt, 1H),7.23-7.27(m, 1H), 7.48-7.58(m, 5H), 7.60(d, 1H), 7.77(td,1H),8.03(d,1H), 8.28(d,1H), 8.38(d,1H), 8.44(dd,1H), 8.64(ddd, 1H), 9.04(d,1H).

ESI-Mass; 402 [M⁺+H]

(383B)

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.33(t, 3H), 3.44(q, 2H), 7.25-7.28(m,1H), 7.49-7.62(m, 6H), 7.78(dd, 1H), 8.14(d, 1H), 8.31(d,1H),8.41(d,1H), 8.51(dd,1H), 8.64(ddd,1H), 9.13(d,1H).

ESI-Mass; 418 [M⁺+H]

Example 3843-(2-Ethylpyridin-5-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

13 mg of3-(2-chloropyridin-5-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-onewas dissolved in 20 ml of dimethylformamide, followed by the addition of10 mg of potassium carbonate and 2 mg of tetrakistriphenylphosphinepalladium. Under stirring at room temperature in nitrogen atmosphere,triethylborane (1.0M tetrahydrofuran solution) was added dropwisethereinto, followed by heating under stirring at 100° C. for 1 hour innitrogen atmosphere. After the reaction mixture was cooled to roomtemperature, water was added thereto, and extracted with ethyl acetate.The organic layer was washed with brine, and then dried over anhydrousmagnesium sulfate. The solvent was evaporated, and the residue waspurified by silica gel chromatography (hexane/ethyl acetate system), togive 4 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.33(t, 3H), 2.87(q, 2H),7.20-7.24(m,2H), 7.44-7.60(m,5H), 7.64-7.70(m,1H), 7.75(td,1H),8.18(dd,1H), 8.25(d,1H), 8.26(d,1H), 8.61(m,1H), 8.84(d,1H).

Example 3853-(2-Chlorophenyl)-5-(4-chlorophenylthio)-1-(3-pyridyl)-1,2-dihydropyridin-2-one

The title compound was synthesized by the method similar to the methodfor Example 188.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.23-7.50(m,8H), 7.52(d,1H),7.55-7.58(m,1H), 7.72(d,1H), 7.86-7.93(m,1H), 8.66-8.76(m,2H).

Example 3863-(2-Cyanophenyl)-5-(1H-benzimidazol-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

The above compound was synthesized by the method similar to the methodfor Example 190.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.22-7.28(m,2H), 7.32-7.50(m,7H),7.54-7.76(m, 4H), 8.20-8.21(m, 1H), 8.28-8.34(m, 1H).

ESI-Mass; 389 [M⁺+H]

Example 3873-(2-Adamantyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

The above compound was synthesized by the method similar to the methodfor Example 178.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.21-2.06(m, 12H), 2.48(s, 2H), 3.25(s,1H), 7.18(ddd, 1H), 7.33-7.52(m, 5H), 7.54(d, 1H), 7.72(td, 1H), 8.09(d,1H), 8.11-8.13(m, 1H), 8.60(ddd, 1H).

Example 3883-(2-Cyanophenyl)-5-(4-methyl-imidazo[4,5-b]pyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one

3 mg of3-(2-cyanophenyl)-5-(1H-imidazo[4,5-c]pyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-onewas dissolved in 3 ml of acetone. To the mixture was added 2 ml ofmethyl iodide, followed by stirring at room temperature overnight. Themixture was evaporated, and the residue was diluted with 1 ml of water.To the mixture was added 20 mg of sodium hydroxide, followed by stirringat room temperature for 4 hours. The reaction solution was extractedwith ethyl acetate. The organic layer was washed with water and brine,dried over anhydrous magnesium sulfate, and filtered. The filtrate wasevaporated, and the residue was purified by silica gel chromatography(NH silica) (hexane/ethyl acetate system), to give 2 mg of the titlecompound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 4.31(s,3H), 7.07(dd,1H),7.43-7.61(m,7H), 7.64(td,1H), 7.72(dd,1H), 7.76(dd,1H), 8.09(d,1H),8.71(d,1H), 8.73(d, 1H).

ESI-Mass; 404 [M⁺+H]

Example 3893-(2-Cyanophenyl)-1-phenyl-5-(3-phenyl-1,2,4-oxadiazol-5-yl)-1,2-dihydropyridin-2-one

31 mg of carboxylic acid, obtained by hydrolyzing3-(2-cyanophenyl)-5-(methoxycarbonyl)-1-phenyl-1,2-dihydropyridin-2-onewas dissolved in 20 ml of dichloromethane, followed by the dropwiseaddition of a solution of 20 mg of oxalyl chloride in dichloromethanunder ice-cooling. A catalytic amount of dimethylformamide was addedthereto, followed by stirring at room temperature for 1 hour in nitrogenatmosphere. The reaction solution was evaporated, and the residue wasdissolved in dichloromethane. The mixture was added dropwise into asolution of 16 mg of benzamidoxime and 0.05 ml of triethylamine intoluene, under ice-cooling. After heating to room temperature, it wasstirred in nitrogen atmosphere overnight. It was heated to 100° C. for 1hour, cooled to room temperature, and then washed with water. Theorganic layer was washed with brine, and then dried over anhydrousmagnesium sulfate. The solvent was evaporated, and 28 mg of the residuewas dissolved in 10 ml of toluene, followed by heating under reflux for5 hours. After cooling to room temperature, the solvent was evaporated,to give 24 mg of the title compound as white crystals.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.40-7.66(m, 9H), 7.68(dd, 2H), 7.80(dd,1H), 8.12(dd, 2H), 8.32(dd, 1H), 8.52(dd, 1H).

Example 3903-(3-Phenyl-1,2,4-oxadiazol-5-yl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

The above compound was synthesized by the method similar to the methodfor Example 389.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.25-7.29(m,2H), 7.46-7.59(m,7H),7.70(d, 1H), 7.81(td, 1H), 8.20-8.23(m, 2H), 8.59(d, 1H), 8.63(ddd, 1H),9.14(d, 1H).

Example 3913-(2-Cyanothiophen-3-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

22 mg of3-(2-formylthiophen-3-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-onewas dissolved in 20 ml of ethanol. To the mixture were added 6.4 mg ofhydroxylamine hydrochloride and 10.1 mg of sodium acetate, followed byheating at 80° C. for 3 hours. After cooling the reaction mixture toroom temperature, it was poured into a saturated aqueous solution ofsodium hydrogen carbonate, followed by extracting with ethyl acetate.The organic layer was washed with brine, and then dried over anhydrousmagnesium sulfate. The solvent was evaporated, and the resulting residue(25 mg) obtained as an oxime compound was dissolved in 10 ml ofdimethylformamide, followed by adding 0.02 ml of triethylamine. Underice-cooling, 43 mg of 1,1′-carbonyldiimidazole was added thereto,followed by stirring at 60° C. for 1 hour. Then, it was cooled to roomtemperature, water was added thereto, and the mixture was extracted withethyl acetate. The organic layer was washed with brine, and then driedover anhydrous magnesium sulfate. The solvent was evaporated, and theresidue was purified by silica gel chromatography (hexane/ethyl acetatesystem), to give 15 mg of the title compound as white crystals.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.23(ddd, 1H), 7.46-7.58(m, 5H),7.59(d,1H), 7.65(d, 1H), 7.77(td, 1H), 7.78(d, 1H), 8.38(d, 1H), 8.57(d,1H), 8.59(ddd, 1H).

ESI-Mass; 356 [M⁺+H]

Example 3923-[2-(5-Oxazolyl)phenyl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

13 mg of3-(2-formylphenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one wasdissolved in 10 ml of methanol. To the mixture were added 11 mg oftosylmethylisocyanide and 8 mg of potassium carbonate, followed byheating under reflux overnight. After the reaction solution was cooledto room temperature, water was added, and the mixture was extracted withethyl acetate. The organic layer was washed with water and brine, andthen dried over anhydrous magnesium sulfate. It was filtered through NHsilica gel and silica gel, and the filtrate was evaporated. Theresulting precipitates were washed with ether and dried, to give 9 mg ofthe title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.98(s, 1H), 7.20(ddd, 1H), 7.36-7.51(m,7H), 7.54(dt, 2H), 7.72(ddd, 2H), 7.84(s, 1H), 8.11(d, 1H), 8.30(d, 1H),8.59(ddd, 1H).

Example 3933-[2-(5-Oxazolyl)thiophen-3-yl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one

The title compound was synthesized by the method similar to the methodfor Example 392.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.14(s, 1H), 7.16-7.76(m, 10H), 7.82(s,1H), 8.16(d, 1H), 8.29(d, 1H), 8.58(d, 1H).

Example 3943-(2-Cyanophenyl)-5-(2-pyridinecarbonyl)-1-phenyl-1,2-dihydropyridin-2-one(394a) α-(2-Methoxypyridin-5-yl)-2-pyridinemethanol

50 ml of a tetrahydrofuran solution containing 3.00 g of2-methoxy-5-bromopyridine was cooled to −78° C., followed by thedropwise addition of 10 ml of n-butyl lithium (1.6M hexane solution).After the completion of the dropwise addition, 1.70 g of picolinealdehyde was immediately added thereto, followed by stirring at −78° C.for 1 hour, to return the mixture slowly to room temperature. To themixture was added a saturated aqueous solution of ammonium chloride, andthen it was extracted with ethyl acetate. The ethyl acetate layer waswashed with water and brine, and then dried over magnesium sulfate. Thesolvent was evaporated, and the resulting residue was purified by silicagel chromatography (ethyl acetate), to give 1.53 g of the title compoundas a pale yellow solid.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.93(s,3H), 5.87(brs,1H), 6.72(d, 1H),7.24(d, 1H), 7.31-7.36(dd, 1H), 7.55-7.59(dd, 1H), 7.74-7.80(dd, 1H),8.21(d, 1H), 8.62(d, 1H).

(394b) 5-(2-Pyridinecarbonyl)-2-methoxypyridine

To a solution of 0.83 g of α-(2-methoxypyridin-5-yl)-2-pyridinemethanolin 20 ml of an acetone was added 1.70 g of activated manganese dioxide,followed by vigorously stirring at room temperature for 30 minutes. Theresulting precipitates were filtered off and washed with acetone. Then,the filtrate was concentrated, to give 0.80 g of the title compound as awhite solid.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 4.04(s, 3H), 6.84(dd, 1H),7.48-7.54(ddd, 1H), 7.89-7.95(ddd, 1H), 8.09(d, 1H), 8.36-8.40(dd, 1H),8.70-8.74(m, 1H), 9.09(d, 1H).

(394c) 5-(2-Pyridinecarbonyl)-1,2-dihydropyridin-2(1H)-one

0.79 g of 5-(2-pyridinecarbonyl)-2-methoxypyridine was dissolved in 5.0ml of 48% hydrobromic acid, and the mixture was stirred at 70° C. for 30minutes. It was ice-cooled, diluted with water and neutralized withpotassium carbonate. The resulting precipitates were collected byfiltration, washed with water and hexane, and dried, to give 0.51 g ofthe title compound as a white powder.

¹H-NMR (400 MHz, DMSO-d₆); δ(ppm) 6.45(d,1H), 7.65-7.70(ddd,1H),7.95-8.00(dd,1H), 8.05-8.20(m,2H), 8.68-8.75(m,2H), 12.17(brs,1H).

(394d)

5-(2-Pyridinecarbonyl)-3-bromo-1,2-dihydropyridin-2(1H)-one

To a solution of 0.23 g of5-(2-pyridinecarbonyl)-1,2-dihydropyridin-2(1H)-one in 2.0 ml ofdimethylformamide was added 0.21 g of N-bromosuccinimide at roomtemperature, followed by stirring for 1 hour. The mixture was dilutedwith water, and the resulting precipitates were collected by filtration,washed with water and dried, to give 0.26 g of the title compound as apale yellow powder.

¹H-NMR (400 MHz, DMSO-d₆); δ(ppm) 7.67-7.71(ddd,1H), 7.99-8.03(ddd,1H),8.04-8.08(dd,1H), 8.47(d,1H), 8.73-8.75(m, 1H), 8.79(brs, 1H),12.72(brs, 1H).

(394e)

5-(2-Pyridinecarbonyl)-1-phenyl-3-bromo-1,2-dihydropyridin-2-one

A suspension of 0.24 g of5-(2-pyridinecarbonyl)-3-bromo-1,2-dihydropyridin-2(1H)-one, 0.23 g ofphenylboronic acid, 0.30 g of copper acetate and 1 ml of triethylaminein 10 ml of tetrahydrofuran was stirred at room temperature overnight.To the mixture were added concentrated aqueous ammonium (3 ml), water(30 ml) and ethyl acetate (100 ml), to separate the organic layer. Itwas washed with water and brine, and then dried over magnesium sulfate.The solvent was evaporated, and the residue was purified by silica gelchromatography (ethyl acetate/hexane), to give 0.21 g of the titlecompound as a white powder.

¹H-NMR (400 MHz, DMSO-d₆); δ(ppm) 7.50-7.60(m,5H), 7.64-7.68(ddd,1H),8.02-8.09(m,1H), 8.57(d, 1H), 8.66-8.70(m, 1H), 9.00(d, 1H).

(394f)

3-(2-Cyanophenyl)-5-(2-pyridinecarbonyl)-1-phenyl-1,2-dihydropyridin-2-one

To a mixed liquid of 200 mg of5-(2-pyridinecarbonyl)-1-phenyl-3-bromo-1,2-dihydropyridin-2-one, 130 mgof 2-(2-cyanophenyl)-1,3,2-dioxaborinate, 400 mg of cesium carbonate and6 ml of dimethylformamide was added 60 mg of tetrakistriphenylphosphinepalladium, followed by stirring at 130° C. for 5 hours in nitrogenatmosphere. After cooling to room temperature, ethyl acetate was addedthereto. The extract was washed with water and brine, and dried overmagnesium sulfate. The solvent was evaporated, and the residue waspurified by silica gel chromatography (ethyl acetate/hexane), to give 45mg of the title compound as a pale yellow powder.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.40-7.58(m,8H), 7.62-7.68(m,1H),7.75-7.78(d,1H), 7.89-7.94(m,1H), 8.11-8.15(d,1H), 8.47(d,1H),8.65-8.68(m,1H), 9.16(d,1H).

Example 3955-(2-Pyridinecarbonyl)-1-phenyl-3-phenyl-1,2-dihydropyridin-2-one

A mixed liquid of 10 mg of5-(2-pyridinecarbonyl)-1-phenyl-3-bromo-1,2-dihydropyridin-2-one, 10 mgof phenylboronic acid, 40 mg of cesium carbonate, 6 mg oftetrakistriphenylphosphine palladium and 1 ml of dimethylformamide wasstirred at 130° C. for 2 hours in nitrogen atmosphere. After cooling toroom temperature, ethyl acetate was added thereto. The extract waswashed with water and brine, and dried over magnesium sulfate. Thesolvent was evaporated, and the residue was purified by silica gelchromatography (ethyl acetate/hexane), to give 6 mg of the titlecompound as a pale yellow powder.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 7.32-7.58(m,8H), 7.75-7.79(m,2H),7.88-7.94(ddd,1H), 8.09-8.13(m,1H), 8.42(d,1H), 8.63-8.66(m,1H), 9.01(d,1H).

Example 3963-(2-Cyanophenyl)-5-(α-hydroxy-2-picolyl)-1-phenyl-1,2-dihydropyridin-2-one

To a solution of 25 mg of3-(2-cyanophenyl)-5-(2-pyridinecarbonyl)-1-phenyl-1,2-dihydropyridin-2-onein 5 ml of methanol was added 2 mg of sodium borohydride underice-cooling. After 30 minutes, the mixture was diluted with a saturatedaqueous solution of sodium hydrogen carbonate, followed by extractingwith ethyl acetate. The ethyl acetate layer was washed with water andbrine, and dried over magnesium sulfate. The solvent was evaporated, andthe residue was purified by silica gel chromatography (ethyl acetate),to give 15 mg of the title compound as a pale yellow powder.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 5.72(brs,1H), 7.32-7.72(m,13H),7.80-7.92 (m, 1H), 8.57-8.65 (m, 1H).

Example 3973-(2-Cyanophenyl)-5-(2-pyridin-2-yl-vinyl)-1-phenyl-1,2-dihydropyridin-2-one

A mixed liquid of 100 mg of3-(2-cyanophenyl)-1-phenyl-5-bromo-1,2-dihydropyridin-2-one, 100 mg of2-vinylpyridine, 6 mg of palladium acetate, 17 mg oftri-(o-tolyl)phosphine and 3 ml of triethylamine was stirred at 130° C.for 2 hours in nitrogen atmosphere. After cooling to room temperature,ethyl acetate was added thereto. The extract was washed with water andbrine, and dried over magnesium sulfate. The solvent was evaporated, andthe residue was purified by silica gel chromatography (ethylacetate/hexane), to give 16 mg of the title compound as a white powder.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 6.95-7.00(d,1H), 7.16-7.21(m,1H),7.26-7.35(m,1H), 7.44-7.60(m,7H), 7.62-7.81(m,5H), 8.03(d,1H),8.57-8.61(m,1H).

Example 3983-[(2-Ethoxycarbonyl)vinylthiophen-3-yl]-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

To a solution of 7.5 mg of ethyl diethylphosphonoacetate intetrahydrofuran was added 1.3 mg of sodium hydride in nitrogenatmosphere under ice-cooling, followed by the dropwise addition of asolution of 10 mg of3-(2-formylthiophen-3-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-onein tetrahydrofuran. After stirring the mixture at room temperature for 1hour in nitrogen atmosphere, water was added thereto. Then, it wasextracted with ethyl acetate. The organic layer was washed with brine,and then dried over anhydrous magnesium sulfate. The solvent wasevaporated, and the residue was purified by silica gel chromatography(hexane/ethyl acetate system), to give 4 mg of the title compound.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 1.28(t,3H), 4.21(q,2H), 6.34(d,1H),7.19-7.23(m,2H), 7.34-7.41(m,2H), 7.43-7.56(m,5H), 7.74(td,1H),7.88(d,1H), 8.00(d,1H), 8.30(d,1H), 8.58-8.60(m,1H).

ESI-Mass; 429 [M⁺+H]

Example 399 5-Bromo-2-methoxypyridine

5-Dibromopyridine (200 g) and 28% sodium methoxide methanol solution(1535 g) were heated under reflux for 30 minutes, followed by cooling toroom temperature. The mixture was partitioned between water (1.6 L) andtert-butylmethyl ether (1.6 L). The resulting organic layer was washedwith brine (1 L) for 3 times, and then dried over anhydrous MgSO₄overnight. The dried organic layer was evaporated at 65° C., to give 160g (96%) of the title compound as a brown oil.

¹H-NMR (400 MHz, CDCl₃); δ(ppm) 3.91(3H, s), 6.66(1H, d), 7.64 (1H, dd),8.20 (1H, d).

MS: MH⁺ 188, 190

Example 400 6-Methoxy-3-pyridylboronic acid

5-Bromo-2-methoxypyridine (152 g) was dissolved in tetrahydrofurananhydride (1520 mL) under stirring in nitrogen atmosphere, followed bycooling to −75.1° C. as bulk temperature. Under cooling and stirring,380 mL of a 2.46 mol/L butyl lithium solution was added dropwisethereinto, followed by the dropwise addition of 192 mL oftrimethoxyborane. The cooling bath was removed 30 minutes aftercompletion of the dropwise addition, and the mixture was stirred at roomtemperature overnight. On the next day, 1.5 L of a 2 mol/L aqueoussolution of hydrochloric acid was added thereto, followed by stirringfor 1.5 hours. Then, it was neutralized with 460 mL of a 5 mol/L aqueoussolution of sodium hydroxide. It was then extracted with 1 L of ethylacetate, and the resulting aqueous layer was extracted again with 1 L ofethyl acetate. The combined organic layer was washed twice with 1 L of10% saline water, dried over anhydrous magnesium sulfate, and thenevaporated, to give 105 g (88%) of the title compound as a slightlyyellowish white solid.

¹H-NMR (CDCl₃, 400 MHz): 3.83(3H,s), 6.74(1H,d), 7.98(1H, dd), 8.10(2H,s), 8.50(1H, s).

Example 401 2-Methoxy-5-pyridin-2-yl-pyridine

6-Methoxy-3-pyridylboronic acid (105 g), 2-bromopyridine (90 g),palladium acetate (3.21 g), triphenylphosphine (15 g), potassiumcarbonate (237 g), 1,2-dimethoxyethane (900 mL) and water (900 mL) wereheated under reflux for 5 hours and 40 minutes under stirring. Aftercooling the reaction solution, ethyl acetate (1 L) was added thereto toextract. The organic layer was washed with 1 L of 10% aqueous solutionof ammonium chloride, 1 L of 10% aqueous ammonia and 1 L of 10% saline,and then evaporated, to give 126 g (87%) of the title compound.

¹H-NMR (CDCl₃, 400 MHz): 4.00(3H,s), 6.85(1H,d), 7.21-7.26(1H,m),7.67(1H,d), 7.75(1H,dt), 8.25(1H,dd), 8.66-8.70(1H,m), 8.74(1H,d).

MS: MH⁺ 187

Example 402 5-Pyridin-2-yl-2(1H)-pyridone

A mixture of 2-methoxy-5-pyridin-2-yl-pyridine (550 g) and a 4 mol/Laqueous solution of hydrochloric acid (2.4 L) was heated under refluxfor 3 hours. After cooling the reaction solution, and washed withtert-butylmethyl ether (2.2 L). To the aqueous layer was added 8 mol/Laqueous solution of sodium hydroxide (1.1 L) under cooling withice-water, and then the mixture was washed twice with tert-butylmethylether (2.2 L). Then, it was adjusted to pH 8 with concentratedhydrochloric acid (310 ml) and 8 mol/L aqueous solution of sodiumhydroxide (100 ml), followed by partitioning between 1-butanol (4.5 L)and brine (1.8 L). The aqueous layer was extracted again with 1-butanol(4.5 L), and the combined organic layer was evaporated at 45-50° C. Tothe resulting residue was added tert-butylmethyl ether (2.2 L), to givecrystals. The resulting crystals were collected by filtration underreduced pressure and air-dried at 60° C. Then, water (1.6 L) was addedthereto to dissolve under heating. Then the mixture was water-cooled,and recrystallized. The resulting crystals were collected by filtrationunder reduced pressure and air-dried at 60° C., to give 188 g (66%) ofthe title compound as grayish white crystals.

¹H-NMR (DMSO-d₆, 400 MHz): 6.42 (1H, d), 7.19-7.26 (1H, m), 7.74-7.81(2H,m), 8.11 (1H,d), 8.17 (1H,dd), 8.52-8.55 (1H,m).

MS: MH⁺ 173

Example 403 1-Phenyl-5-pyridin-2-yl-2(1H)-pyridone

While stirring 5-Pyridin-2-yl-2(1H)-pyridone (185 g), PhB(OH)₂(261 g),Cu(OAc)₂(19.4 g), pyridine (173 ml) and DMF (1480 ml) at roomtemperature, air was blown at 2.0 L/minute therein, to initiate thereactions. Since 26% of the reactant remained unreacted 7 hours afterthe initiation of the reaction, flow of air was stopped to suspend thereactions. On the next day, air was blown into the solution to restartthe reactions, and the reactant was consumed to 0.57% of the initialweight in 5.5 hours. The reaction solution was poured into ice-cooled10% aqueous ammonia (7.5 L), to give MA045. The resulting precipitateswere collected by filtration under reduced pressure, and washed withwater (3 L). The resulting crystals were suspended into 10% aqueousammonia (3.6 L) under stirring at room temperature for 1 hour. Then thecrystals were collected by filtration under reduced pressure, and washedwith water (2 L). The resulting crystals were air-dried overnight, togive 187 g (68%) of the title compound as brown crystals.

¹H-NMR (CDCl₃, 400 MHz): 6.77(1H,d), 7.19(1H,dd), 7.42-7.48(3H,m),7.49-7.55(3H, m), 7.72(1H, dt), 8.04(1H, dd), 8.21(1H, d), 8.57-8.59(1H,m).

MS: MH⁺ 249

Example 404 3-Bromo-1-phenyl-5-pyridin-2-yl-2(1H)-pyridone

1-Phenyl-5-pyridin-2-yl-2(1H)-pyridone (186 g), N-bromosuccinimide(141.7 g) and N,N-dimethylformamide (900 ml) were stirred at roomtemperature. After 2.5 hr, 6.45 g of NBS was added thereto. Afterdepletion of the reactant was confirmed, the reaction solution waspoured into water (4.5 L) under ice-cooling, followed by stirring in acold-room (approximately 4° C.) overnight. The resulting crystals werecollected by filtration under reduced pressure, followed by dissolvingin IPA (3.25 L) and H₂O (650 ml) under heating. After the completedissolution was confirmed, the solution was left to cool gradually, andthen ice-cooled. Then, the mixture was stirred in a cold-room overnight.The resulting crystals were collected by filtration under reducedpressure and air-dried at 60° C., to give 191 g (81%) of the titlecompound.

¹H-NMR (CDCl₃, 400 MHz): 7.19-7.24 (1H, m), 7.42-5.56 (6H, m), 7.74 (1H,dt), 8.19 (1H, d), 8.51 (1H, d), 8.58-8.61 (1H, m).

MS: MH⁺ 327, 329

Among the above Examples, the particularly preferable compounds include

-   3-(2-cyanophenyl)-5-(2-methylsulfonylaminophenyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-chloro-3-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-nitrophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-aminophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-methylsulfonylaminophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-methylaminophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-dimethylaminophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-[3-(5-methoxymethyl-2-oxazolidinon-3-yl)-phenyl]-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-methoxycarbonylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-methylaminocarbonylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyano-3-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-(4-hydroxyphenyl)-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-(4-dimethylaminoethoxyphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-formylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-hydroxymethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-cyanomethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-acetylaminomethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-methylsulfonylaminomethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-acetoxymethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-methylthiophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-methylsulfonylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-formylthiophen-3-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-diethylaminomethylthiophen-3-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-hydroxymethylthiophen-3-yl)-1-phenyl-1,2-dihydropyridine-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-benzyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-phenyl-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1,5-diphenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-methoxyphenyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(3,4-dimethoxyphenyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(thiophen-3-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-fluorophenyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(thiophen-2-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(3-furfuryl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-furfuryl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-on,-   3-(2-methoxycarbonylphenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-phenyl-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-fluorophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-(3-methoxyphenyl)-1,2-dihydropyridin-2-one;-   3-(2-fluoro-3-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(4-methoxy-3-pyridyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-fluoro-3-pyridyl)-5-(2-pyridyl)-1-(3-methoxyphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-fluorophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-fluorophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-fluorophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-methoxyphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-methoxyphenyl)-1,2-dihydropyridin-2-one;-   3-phenyl-5-(2-pyridyl)-1-(3-fluorophenyl)-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-(4-fluorophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-formylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-formylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-chlorophenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-tolyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-trifluoromethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(thiophen-3-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-furfuryl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-tolyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-trifluoromethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-methoxypyridin-5-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(pyrimidin-5-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-benzyloxymethylpyridin-5-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-ethylthiopyridin-5-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(3-methoxypyridin-5-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-chloropyridin-5-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-fluoropyridin-5-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-methoxyphenyl)-1,2-dihydropyridin-2-one;-   3-phenyl-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one;-   3-(thiophen-3-yl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2,6-dimethylphenyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanothiophen-3-yl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-fluoro-3-pyridyl)-5-(2-pyridyl)-1-(3-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-(3-hydroxyphenyl)-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-(3-dimethylaminoethoxyphenyl)-1,2-dihydropyridin-2-one;-   3-(2-chlorophenyl)-5-(2-pyridyl)-1-(3-dimethylaminopropoxyphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-hydroxymethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(4-cyanomethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-cyanomethylphenyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(6-diethylaminomethyl-2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-phenyl-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one;-   3-(2-hydroxypyridin-6-yl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   1-(2-aminobenzothiazol-6-yl)-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(1-benzyl-1,2,3,6-tetrahydropyridin-5-yl)-1,2-dihydropyridin-2-one;-   3-[2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(6-methylpyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(5-methylpyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(3-hydroxypyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-phenyl-5-(2-thiazoyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-methoxypyridin-6-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   1-(4-aminophenyl)-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   1-(3-aminophenyl)-3-(2-cyanophenyl)-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-aminotoluen-4-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-[3-(dimethylaminoethoxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-[3-(piperidinoethoxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-[3-(pyrrolidinoethoxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-[3-(diisoproylaminoethoxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-[3-(4-piperidinobutyl-1-oxy)phenyl]-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-(4-nitrophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   1-phenyl-5-(2-pyridyl)-3-(2-thiazoyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-(3-pyridyl)-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one;-   3-(2-fluoropyridin-3-yl)-1-phenyl-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanopyridin-3-yl)-1-phenyl-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-(3-nitrophenyl)-5-(2-pyrimidinyl)-1,2-dihydropyridin-2-one;-   3-(2-nitrophenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-formylthiophen-3-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-naphthyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(1-naphthyl)-1,2-dihydropyridin-2-one;-   5-(2-aminopyridin-6-yl)-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one;-   5-(2-bromopyridin-6-yl)-3-(2-cyanophenyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-morphorinopyridin-6-yl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-(3-hydroxyphenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-[3-(4-piperidyloxy)]phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   1-[3-(N-acetylpiperidin-4-yl-oxy)phenyl]-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-1-{3-[1-(methanesulfonyl)piperidin-4-yl-oxy]phenyl}-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   1-[3-(N-methylpiperidin-4-yl-oxy)phenyl]-3-(2-cyanophenyl)-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-(6-chloro-1H-benzimidazol-2-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-(2-cyanophenyl)-5-(2-pyridyl)-1-(2-nitrotoluen-4-yl)-1,2-dihydropyridin-2-one;-   3-(2-cyanothiophen-3-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one;-   3-[2-(5-oxazolyl)phenyl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one;-   3-[2-(5-oxazolyl)thiophen-3-yl]-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one;    and-   3-[(2-ethoxycarbonyl)vinylthiophen-3-yl]-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one.

Example a b c 1

2

3

4

6 H

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

68

69

70

71

72

73

74

75

76

77

78

79

80

81

82

83

84

85

86

87

88

89

90

91

92

93

94

95

96

97

98

99

100

101

102

103

104

105

106

107

108

109

110

111

112

113

114

115

116

117

118

119

120

121

122

123

124

125

126

127

128

129

130

131

132

133

134

135

136

137

138

139

140

141

142

143

144

145

146

147

148

149

150

151

152

153

154

155

156

157

159

160

162

163

164

165

166

171

172

173

177

178

180

182

183

184

186

189

190

191

192

193

194

195

196

197

198

199

200

201

202

203

204

205

206

207

208

209

210

211

212

213

214

215

216

217

218

219

220

221

222

225

226

227

228

229

230

231

232

233

234

235

236

237

238

239

240

241

242

243

244

245

246

247

248

249

250

251

252

253

254

255

256

257

258

259

260

261

262

263

264

265

266

267

268

269

270

271

272

273

274

275

276

277

278

279

280

281

282

283

284

285

286

287

288

289

290

291

292

293

294

295

296

297

298

299

300

301

302

303

304

308

315

320

324

325

326

327

328

330

333

334

337

338

341

342

343

351

352

353

354

355

356

357

358

359

360

361

362

363

364

365

366

367

368

369

370

371

372

373

374

375

376

377

  378-A)

   378-B)

  379-A)

   379-B)

380

381

  383-A)

   383-B)

384

386

387

388

389

390

391

392

393

398

Example a b c x¹ 31

—CH₂— 158

—CH₂CH₂— 316

317

—CH₂— 318

—CH₂— 319

—CH₂— 329

—CH₂— 331

—CH₂— 332

—CH₂— 335

—CH₂— 336

—CH₂— 339

—CH₂— 340

—CH₂—

Example a b c x2 161

—C≡C— 168

169

170

174

175

176

179

187

188

—S— 223

306

310

311

312

314

321

322

323

344

346

347

348

349

382-A

382-B

Example a b c x3 181

185

224

307

309

313

345

350-A

350-B

385

—S— 394

395

396

397

Example a b c d 167

CH₃— 305

CH₃—

Test Example 1

The suppressing action of the compounds of the present invention tocalcium influx into nerve cells induced by AMPA was investigated usingthe primary culture system of nerve cells of cerebral cortex of embryoof rat.

Culturing Conditions:

Cerebral cortex was cut out from the brain of rat of gestational 18 daysand treated with trypsin and DNase to disperse the cells. The cells wereflown by MEM containing 10% of serum, sown in a culture bottle andastrocytes were proliferated. The astrocytes were re-dispersed bytrypsin and sown in a 96-well plate. After incubation for one week, itwas confirmed that the astrocytes covered all over the bottom and thenthe nerve cells of cerebral cortex which was dispersed by the abovemethod were sown thereupon. After incubation for 24 hours, the mediumwas changed, the incubation was carried out for one week and, afterthat, the medium was changed to that containing 1 μM of MK-801. Nervecells which were incubated for not shorter than 8 to 10 days were used.

Suppressing Action to Calcium Influx into Nerve Cells Induced by AMPA

Calcium influx into the cells was measured using Fura2-AM which was acalcium-sensitive fluorescent dye. It was treated in a medium containingFura2-AM for 1 hour, incorporated into the cells, exchanged to a Tyrodesolution containing 1 μM MK-801 and stimulation was carried out using 2μM AMPA. Change in the amount of calcium flown into the cells weremeasured as the change in the fluorescent intensity at the exciting wavelength of 340/380 nm. Effect of the test compound was evaluated usingthe reaction resulted in the AMPA added to a Tyrode solution containingno compound as a control. Results are shown in Tables 1 to 3.

GYKI 52446(LePeillet, et al., Brain Res., 571, 115, 1992) was used as acontrol compound. IC₅₀ of GYKI 52466 was 9.02 μM.

Test Example 2

Anticonvulsant Action Induced by AMPA

A test compound was suspended in a 0.5% methyl cellulose solution or insesame oil and was orally administered (25 mg/kg) to male mice of ddystrain. After 30 minutes or 1 hour from the oral administration, AMPAwas continuously injected (2 nmole/5 μl/minute/mouse) into lateralventricle to induce the convulsions. The effect was judged by atime-extending action until the convulsion takes place by a continuousinjection of AMPA.

Results

The compound represented by the above formula (I) according to thepresent invention showed an excellent anticonvulsant action. Forexample, the compounds of Examples 4, 7, 9, 12, 16, 32, 41, 47, 57, 61,76, 78, 91, 126, 128, 137, 139, 164, 199, 261, 262, 264, 270 and 298showed a significant anticonvulsant action.

Test Example 3

Occlusion Model of Midcerebral Arteries

The usefulness of the compound related to the present invention in theremedy of cerebral vascular accident acute stage was confirmed by thetest below. Namely, the cerebral bloodstream of midcerebral arteries wasblocked by inserting a nylon suture thread of 4-0 specification whoseedge was crashed with flame, by 17 mm from the branch of internalcarotid artery, through internal carotid artery from the externalcarotid artery of a male Sprange Dawley rat, and cerebral infarction wasprepared (Zea Longa et al., Storke 20:84-91, 1989). The size of thecerebral infarction was evaluated by preparing the intersection slice ofbrain having a thickness of 2 mm and measuring the area of a portionwhich was not stained by TTC staining. The effect of the testedsubstance was carried out in this model by comparing the infarctionnidus size between a group treated with a solvent and a group treatedwith the tested substance.

As a result, the compound related to the present invention revealed anexcellent effect as the therapeutic agent of cerebral vascular accidentacute stage.

Test Example 4

Antimethamphetamine Effect

(S)—(+)—N, α-dimethylphenetylamine (hereinafter, referred to as“methamphetamine”) was dosed intraperitoneal injection to a rat or mouseto which the tested compound was dosed, and a quantity of activemovement was measured using an active movement measuring apparatus(SCANET SV-10; manufactured by TOYO Sangyo Co., Ltd.). The activity asthe therapeutic agent of schizophrenia was evaluated using thehyperdynamic effect control of active movement caused by methamphetamineas an index (K. E. Vanover, Psychopharmacology 136: 123-131, 1998). Theeffect of the tested substance was confirmed by the control effect of aquantity of active movement accentuation in comparison with the groupdosed with a solvent.

As a result, the compound related to the present invention revealed anexcellent methamphetamine effect.

Test Example 5

Rigidity Model of Intercaruncle Ablatio Provocative Muscle

An animal model in which the myotony of anteroposterior limbs wasprovoked was prepared by electrically freezing between the upper cumulusand the lower cumulus of a rat. Myorelaxation effect was evaluated basedon the effect of controlling the increase of muscle discharge which isgenerated when the posterior limbs in this model are moved back andforth. The effect of the tested substance was confirmed by the changesof muscle discharge amount before dosing the tested substance and muscledischarge amount after dosing it.

The compound related to the present invention revealed an excellentmyorelaxation effect.

Test Example 6

Light Dark Test

A mouse is put in a dark box which is composed of two light and darkboxes which are linked by a tunnel, and items below were recordedconcerning the behavior of the mouse for 5 minutes after that.

-   1. A time for remaining in the light and dark boxes.-   2. Times by which the mouse went and came back between the light box    and the dark box.-   3. Times by which the mouse went until the entrance of the light    box.

The antianxiety effect of the tested compound was detected as theelongation of the time remaining in the light and dark boxes, theincrease of times by which the mouse went and came back between thelight box and the dark box, and the increase of times by which the mousewent until the entrance of the light box, for the group dosed with asolvent (Hascoet M., Bourin M., Pharm. Biochem. Behav. 60: 645-653,1998).

According to the present test, it was confirmed that the compoundrelated to the present invention has an excellent antianxiety effect.

Test Example 7

Destruction model of 6-hydroxydopamine-inductive nigrostriaton

10 mg/kg of L-Dihydroxyphenylalanine (L-DOPA) (twice per day) was dosedevery day in the abdomen of a rat whose one side of nigra neurocyte wasdestroyed by injecting 6-hydroxydopamine (6-OHDA) into nigra, thereforethe increase of rotational motion to the reverse side of encephalopathywas provoked (C. Marin et al, Synapse 36(4):267-274, 2000). After thesolvent or the tested compound was dosed to the rat, influence on theprovoked rotational motion was studied. The tested compound delayed thetime until primitive rotational motion shows the maximum value afterdosing L-DOPA, and increased the time of showing rotation which is ahalf or more of the maximum rotational number.

Test Example 8

Acetic Acid Writhing Method

Anguishing condition under which the lower half of rat's body wastwisted, its abdomen was dented and its hind legs were extended wasprovoked by injecting 0.6% acetic acid saline in the abdomen of therats. After the tested compound and the solvent were dosed, the aceticacid saline was injected in the abdomen, and analgesic effect wasevaluated by comparing the times of these abnormal actions within anobservation time (5 to 15 minutes after the dose of acetic acid) whichoccur after the dosing (Basic Pharmacology Experiment, edited byKazuhiko Kubota, pages 45-47, Nankoh-do).

As a result, it could be confirmed that the compound related to thepresent invention controls the times of the abnormal actionssignificantly and has an excellent analgesic effect.

Test Example 9

Vomiting Model Induced by Cisplatin

A catheter for venoclysis was buried in a ferret, and the rat waspostoperatively recovered. Then, vomiting reaction was provoked byinjecting 10 mg/kg of cis-diaminedichloroplatinum (cisplatin) (A.Fink-Jensen et al., Neuroscience Letters 137: 173-177, 1992). Cisplatin(10 mg/kg) was injected a ferret which was preliminarily treated withthe tested compound or the solvent, then the ferret was put in anobservation cage, and the time (latent time) and times until therhythmical contraction of abdomen (defined as vomiting) occurs duringthe observation period of 240 minutes were measured.

As a result, the compound related to the present invention reduced thelatent time and the vomiting times significantly.

Test Example 10

Experimental Autoimmune Encephalomyelitis Model

Female Lewis rats (205±10 g) obtained from Charles River, Kent UK, werehoused in pairs under environmentally controlled conditions (6:00a.m.-6:00 p.m. light/dark cycle; 22-24° C.; 45-55% humidity) and allowedfree access to food and water. Experimental groups consisted of 9-12animals. Rats were immunised in each hind foot with 20-50 μl of inoculumcontaining 50 μg guinea pig myelin basic protein (MBP; finalconcentration 2 mg/ml), emulsified in Freund's complete adjuvant (CFA;Sigma, UK) containing Mycobacterium tuberculosis H37Ra (finalconcentration 5.5 mg/ml; Difco Laboratories, UK). Animals were weighedand monitored daily and clinical disease scored as (0) no clinicalsigns; (1) flaccid tail and weight loss; (2) hind limb hypotonia withfurther weight loss; (3) complete hind limb paralysis; (4) paraplegiaand (5) death. In addition, intermediate scores were assigned to animalswhich showed a loss of tonicity in the distal half of the tail(score=0.5), paralysis of one hind limb (score=2.5) or complete hindlimb paralysis with forelimb weakness (score=3.5). During the period ofcompound administration (10-16 days post immunisation; dpi) animals werescored 15 h after injection of vehicle or compound to avoid any acuteeffect of treatment on disease score. Compounds were dissolved/suspendedin 0.5% methyl cellulose using a hand held Polytron homogeniser (PT1200;2 min). Rats were dosed p.o. with either methyl cellulose vehicle (2.5ml/kg) or compound at 5, 10 and 20 mg/kg.

Results: the compound of the invention is improved in view ofexperimental autoimmune encephalomyelitis. The compounds of Examples 7,32, 76, 139, 164, 261, 262 and 264 are for example provided with asuperior effect to the vehicle-administered group.

TABLE 1 Example IC₅₀ (μM) 1 0.8 2 1.8 3 0.3 4 0.1 5 0.6 6 9.3 7 0.1 80.1 9 0.03 10 0.05 11 0.06 12 0.1 13 0.2 14 0.1 15 0.05 16 0.1 17 0.7 180.02 19 0.08 20 0.04 21 0.03 22 0.06 23 0.2 24 0.2 25 0.03 26 0.02 270.05 28 0.2 29 0.1 30 0.04 31 0.1 32 0.1 33 0.7 34 3.7 35 3.1 36 1.1 370.7 38 6.3 39 0.3 41 0.08 42 0.2 43 0.5 44 0.3 45 0.2 46 0.4 47 0.6 480.04 49 0.2 52 1.1 55 0.8 56 3.2 57 0.2 58 0.1 60 1.7 61 0.2 62 3.1 631.1 64 2.8 65 0.6 66 2.4 67 6.5 69 0.9 70 3.1 71 0.05 72 0.7 73 1.2 740.2 76 0.1 77 0.02 78 1.4 79 2.6 80 0.3 81 2.7 82 0.8 84 0.9 86 1.9 871.2 88 0.3 90 0.7 91 0.05 92 0.05 93 1.9 94 1.5 95 0.3 96 0.06 97 0.4 980.6 99 0.1 100 0.4 101 0.2 102 0.02 103 0.03 104 0.2 105 0.03 106 0.07107 0.07 108 0.03 109 0.01 110 2.0 111 0.4 112 0.6 113 1.2 114 0.6 1150.06 116 0.2 117 0.4 118 0.1 119 1.7 120 0.2 121 0.6 123 0.2 124 0.7 1260.3 127 0.4 128 0.07 129 2.6 130 0.9 131 3.7 132 3.1 133 0.3

TABLE 2 Example IC₅₀ (μM) 135 0.04 137 0.05 139 0.3 140 6.6 141 0.7 1422.2 143 0.1 144 0.01 146 0.2 147 1.6 148 0.8 149 0.1 150 0.3 151 0.3 1524.0 154 5.0 157 0.5 159 1.6 163 8.2 164 0.08 165 0.4 166 0.3 171 2.3 1734.2 174 3.3 176 5.4 178 2.0 180 0.5 182 6.0 184 2.3 185 1.7 187 6.1 1888.5 190 0.6 192 1.1 193 0.4 195 0.2 196 0.3 197 2.9 198 0.3 199 0.7 2002.0 201 0.2 202 0.7 204 1.6 206 0.5 209 7.0 210 5.2 211 3.6 215 0.1 2162.4 217 1.3 218 0.1 219 3.7 220 0.6 221 7.1 222 0.2 226 9.5 227 1.8 2282.7 229 4.2 230 4.0 232 4.3 234 0.9 235 4.4 236 0.6 237 1.5 238 0.6 2390.3 240 0.1 241 0.4 242 0.5 243 1.2 244 1.8 245 1.2 246 1.1 247 3.6 2483.4 249 0.3 250 0.9 251 0.9 252 0.3 253 4.7 255 0.5 256 1.2 257 3.7 2592.0 260 2.7 261 0.08 262 0.3 263 1.0 264 0.05 265 0.7 266 0.1 267 1.0268 4.2 269 1.9 270 0.14 272 3.3 275 6.1 276 1.9 277 0.6 278 2.8 279 3.7280 1.3 282 9.0 284 2.8 285 7.2 286 0.3 287 5.6 288 1.2 290 0.2 291 0.14292 3.3 293 3.3 294 0.6 297 4.2 298 0.3 299 4.4 300 0.3

TABLE 3 Example IC₅₀ (μM) 302 0.3 303 0.9 307 2.0 308 1.6 309 4.1 3135.9 314 4.6 315 0.08 316 2.1 317 0.6 318 3.1 319 2.0 320 2.3 321 4.0 3260.9 327 8.0 330 0.4 333 0.3 334 0.6 337 0.7 338 0.4 341 0.2 342 1.3 3423.2 344 4.7 346 3.7 351 3.3 352 1.6 354 1.5 355 0.2 356 2.1 358 1.4 3592.3 360 3.1 362 3.7 365 2.7 367 0.6 371 0.6 379-B 6.4 381 0.4 382-B 2.3385 1.1 386 3.5 387 7.0 388 2.9 390 1.0 391 0.1 392 0.1 393 0.3 394 1.4395 0.9 398 0.2

1. A compound represented by the following formula, a salt thereof or ahydrate thereof

wherein A^(1a) and A^(3a) are the same as or different from each otherand each indicates optionally substituted C₆₋₁₄ aromatichydrocarbocyclic group or 5 to 14-membered aromatic heterocyclic group;and R indicates hydrogen atom or a halogen atom.
 2. The compoundaccording to claim 1, a salt thereof or a hydrate thereof, whereinA^(1a) and A^(3a) are the same as or different from each other and eachrepresents optionally substituted phenyl group, pyridyl group,pyridazinyl group, pyrimidinyl group, pyrazinyl group, thienyl group,thiazolyl group, furyl group, naphthyl group, quinolyl group,isoquinolyl group, indolyl group, benzimidazolyl group, benzothiazolylgroup, benzoxazolyl group, imidazopyridyl group or carbazolyl group. 3.The compound according to claim 1, a salt thereof or a hydrate thereof,wherein A^(1a) and A^(3a) are the same as or different from each otherand each represents optionally substituted phenyl group, pyridyl group,pyrimidinyl group, thienyl group or furyl group.
 4. The compoundaccording to claim 1, a salt thereof or a hydrate thereof, wherein R isa hydrogen atom or bromine.
 5. The compound according to claim 1, a saltthereof or a hydrate thereof, wherein A^(1a) is an optionallysubstituted C₆₋₁₄ aromatic hydrocarbocyclic group, A^(3a) is anoptionally substituted 5 to 14-membered aromatic heterocyclic group, andR is a halogen atom.
 6. The compound according to claim 5, a saltthereof or a hydrate thereof, wherein the compound is3-bromo-1-phenyl-5-pyridin-2-yl-2(1H)-pyridone.